TW202104221A - Compounds and methods for ep300 or cbp modulation and indications therefor - Google Patents

Abstract

Disclosed are compounds of Formula I:

or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein A¹ , A² , A³ , A⁴ , R⁴ , X¹ , X² , and X³ are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.

Description

Compounds and methods for EP300 or CBP regulation and its indications

Cross reference of related applications

This application claims the rights under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62/831,622 filed on April 9, 2019, which is incorporated herein by reference in its entirety.

The present invention relates to organic compounds, which are suitable for treatment in mammals, and are especially used to modulate EP300 or CBP for various diseases associated with the overexpression of EP300 or CBP.

Adenovirus E1A-related 300 kDa protein (EP300, also known as P300 or KAT3B) and CREB binding protein (CBP, also known as CREBBP or KAT3A) have a homologous bromine domain containing a transcription co-activator, which is assembled with other proteins to Causes the initiation of specific gene expression. More specifically, EP300 and CBP are histone acetyltransferases (HAT), histone and non-histone proteins whose acetylation plays a role in gene expression regulation, transcription and cell cycle regulation. The acetylation status of lysine residues in the tails of histones is one of a variety of epigenetic post-translational modifications that change the DNA templated process, such as transcription, to promote malignant transformation. Protein acetylation also helps block polyubiquitination, thereby preventing proteasome degradation and cell death. (Giotopoulos et al. "The epigenetic regulators CBP and p300 facilitate leukemogenesis and represent therapeutic targets in acute myeloid leukemia)", "Oncogene ( Oncogene), January 21, 2016; 35(3): 279-289). The bromodomain, including BDR4, is a reader of the acetyl tag in the histone tail. It is written by EP300/CBP. Therefore, the bromodomain, EP300 and CBP all share the same pathway in the regulation of gene transcription (Perez -Salvia et al., "Bromodomain inhibitors and cancer therapy: From structures to applications", "Epigenetics & Chromatin", 2018, 11:30). These proteins interact with many other proteins involved in transcription and cell cycle regulation, as well as the products of oncogenes and fusion genes (Giotopoulos et al., 2016).

It has been found that the inhibition of CBP or EP300 has an inhibitory effect on the growth of acute myeloid leukemia cells, and EP300 and CPB are promising therapeutic targets across multiple subtypes of acute myeloid leukemia (AML) (Giotopoulos et al., 2016). An inactivating mutation of the acetyltransferase gene in B-cell lymphoma has also been reported (Mullighan et al., "CREBBP mutations in relapsed acute lymphoblastic leukemia", "Nature ( Nature) )", 2011; 471(7337): 235-9).

It has also been reported that due to the direct transcriptional inhibition of lymphocyte-specific transcription factor IRF4 (which is necessary for the survival of myeloma cells), CPB or EP300 inhibition can eliminate the viability of multiple myeloma cell lines, and CBP/EP300 inhibition is useful A feasible therapeutic strategy for targeting multiple myeloma and other lymphoid malignancies that depend on the IRF4 network (Conery et al., the transcriptional co-activator CBP/CBP/ as a therapeutic strategy targeting the IRF4 network in multiple myeloma Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma, https://doi.org/10.7554/eLife.10483.001).

EP300 inhibition can also stimulate autophagy to produce anti-aging effects. For example, spermidine is a polyamine agent that acts as an EP300 inhibitor that stimulates autophagy to produce anti-aging effects to delay age-related diseases and death (Madeo et al., "Spermidine Delays Human Aging (" Spermidine delays ageing in humans, "Aging", 2018, Vol. 10, No. 8).

It has also been shown that the inhibition of CBP or EP300 can down-regulate the expression of AR (androgen receptor)-dependent cancer cells, and this has been confirmed in AR-dependent prostate cancer cell lines and AR-dependent breast cancer tumors (Garcia-Carpizo et al., " CREBBP/EP300 bromodomain inhibitors in breast cancer, "Mol. Cancer Res., 17(3), March 2019).

Therefore, compounds that can inhibit EP300 or CBP represent a new class of potential therapeutic agents capable of regulating histone acetyltransferase (HAT), the histone acetyltransferase acetylated histones and non-histone proteins . Since there are no EP300 or CBBP inhibitors currently approved for the treatment or prevention of diseases in humans, there is still a need for new compounds capable of modulating EP300 or CBP.

An embodiment of the present invention relates to a new compound, as described in any of the embodiments herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof Or deuterated analogs, where these new compounds can modulate EP300 or CBP.

其中A¹ 、A² 、A³ 、A⁴ 、R⁴ 、X¹ 、X² 或X³ 係如本發明中所描述之實施例中之任一者中所描述。Another embodiment of the present invention relates to compounds of formula I:

Wherein A ¹ , A ² , A ³ , A ⁴ , R ⁴ , X ¹ , X ² or X ³ are as described in any of the embodiments described in the present invention.

In the present invention, other embodiments and sub-embodiments of Formula I are further described herein.

Another embodiment of the present invention relates to a pharmaceutical composition comprising a compound of formula I or in the present invention, any embodiment and sub-embodiment of formula I described herein, or any of these compounds One is a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog, and a pharmaceutically acceptable carrier or excipient.

Another embodiment of the present invention relates to a pharmaceutical composition comprising a compound of formula I or in the present invention, any embodiment of formula I described herein or the pharmacology of any of these compounds The above acceptable salts, solvates, tautomers, stereoisomers or deuterated analogs, and another therapeutic agent.

Another embodiment of the present invention relates to a method for treating an individual suffering from a disease or condition mediated by EP300 or CBP, the method comprising administering to the individual an effective amount of a compound of formula I or the compound of the present invention Any embodiment of Formula I described or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog of any of these compounds, or as in the present invention The pharmaceutical composition of any one of the described compounds, wherein the disease or condition comprises abnormal or other manifestations of EP300 or CBP or an activating mutation or translocation of any of the foregoing.

Other embodiments are further described in the detailed description of the present invention.

I. definition

As used in this article, unless expressly indicated otherwise, the following definitions shall apply:

It should be noted herein that, as used herein and in the appended claims, unless the context clearly indicates otherwise, the singular forms "a" and "the" include multiple references.

Unless the point of connection is indicated in other ways, the chemical parts listed in the definition of the variables of formula I of the present invention and all examples thereof should be read from left to right, where the right side is directly connected to the parent structure as defined. However, if the chemical moiety (for example, -alkyloxy-(C ₁ -C ₂₅ )alkyl) is displayed on the left side of the connection point (for example, a dash "-"), then the left side of this chemical moiety is directly connected to as defined The mother part.

It is assumed that when the general description of the compounds described herein is considered for the purpose of constructing the compound, such construction leads to the creation of a stable structure. That is, those skilled in the art will recognize that in theory, some constructs will generally not be regarded as stable compounds (that is, sterically practical and/or synthetically feasible).

Unless otherwise specified, "alkyl" alone or as part of another substituent means a straight or branched chain hydrocarbon having the specified number of carbon atoms (ie, C _1-6 means one to six carbons). Representative alkyl groups include straight and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms. Other representative alkyl groups include straight and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tertiary butyl, isobutyl, second butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl Base and its analogues. For each of the definitions herein (for example, alkyl, alkoxy, arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, heteroarylalkyl, etc.), the prefix is not included When the number of carbon atoms in the alkyl moiety is indicated, the alkyl moiety or its part has 12 or less main chain carbon atoms, or 8 or less main chain carbon atoms, or 6 or less main chain carbon atoms carbon atom. For example, C _{1-6 alkyl refers to a straight or branched chain hydrocarbon with 1 , 2} , 3, 4, 5 or 6 carbon atoms and includes (but is not limited to) -CH 3, C 2 alkyl, C ₃ alkyl, C ₄ alkyl, C ₅ alkyl, C ₆ alkyl, C _1-2 alkyl, C ₂ alkyl, C ₃ alkyl, C _1-3 alkyl, C _1-4 alkyl , C _1-5 alkyl, C _1-6 alkyl, C _2-3 alkyl, C _2-4 alkyl, C _2-5 alkyl, C _2-6 alkyl, C _3-4 alkyl, C _3-5 alkyl, C _3-6 alkyl, C _4-5 alkyl, C _4-6 alkyl, C _5-6 alkyl, and C ₆ alkyl. Although it should be understood that the substitution is attached at any available atom to produce a stable compound, when the optionally substituted alkyl group is such as -OR (e.g., alkoxy), -SR (e.g., sulfanyl), -NHR (e.g., alkane) When the R group of the part of -C(O)NHR and the like, the substitution of the alkyl R group makes any O, S or N bonded to the part (except where N is heteroaromatic Excluding any O, S, or N (except where N is a heteroaryl ring atom) of the substituent and any O, S, or N alkane bound to the moiety Substituents combined with the base carbon.

"Alkylene" alone or as part of another substituent means a linear or branched saturated divalent hydrocarbon moiety derived from an alkane having the number of carbon atoms indicated in the prefix. For example, (that is, C _1-6 means one to six carbons; C _1-6 alkylene means including methylene, ethylene, propylene, 2-methyl propylene, pentylene Group, hexylene and similar groups). C _1-4 alkylene includes methylene -CH ₂ -, ethylene -CH ₂ CH ₂ -, propylene -CH ₂ CH ₂ CH ₂ -and isopropyl -CH(CH ₃ )CH ₂ -, -CH ₂ CH(CH ₃ )-, -CH ₂ -(CH ₂ ) ₂ CH ₂ -, -CH ₂ -CH(CH ₃ )CH ₂ -, -CH ₂ -C(CH ₃ ) ₂ -CH ₂ -CH ₂ CH(CH ₃ )-. Generally, the alkyl group (or alkylene group) will have 1 to 24 carbon atoms, and groups with 10 or fewer, 8 or fewer, or 6 or fewer carbon atoms. When the prefix used to indicate the number of carbon atoms in the alkylene moiety is not included, the alkylene moiety or a portion thereof will have 12 or less main chain carbon atoms, or 8 or less main chain carbon atoms , 6 or fewer main chain carbon atoms, or 4 or fewer main chain carbon atoms, or 3 or fewer main chain carbon atoms, or 2 or fewer main chain carbon atoms, or 1 Carbon atoms.

"Alkenyl" refers to a straight chain monovalent hydrocarbon group or a branched chain monovalent hydrocarbon group having the number of carbon atoms indicated in the prefix and containing at least one double bond. For example, C ₂ -C ₆ alkenyl is meant to include vinyl, propenyl and the like. "C ₂ -C ₆ alkenyl C ₁ -C ₆ alkylene group" is the group -C ₁ -C ₆ alkylene group -C ₂ -C ₆ alkenyl group, wherein the alkenyl group and the alkylene group are as described herein definition.

The term "alkenylene" refers to a straight or branched chain divalent hydrocarbon group containing at least one double bond and having the number of carbon atoms indicated in the prefix.

The term "alkynyl" refers to a monovalent unsaturated hydrocarbon, which in some embodiments is derived from 2 to 20 carbon atoms (in some embodiments, 2 to 10 carbon atoms, for example, 2 to 6 carbon atoms) and has 1 to 6 carbon-carbon parametric bonds, for example 1, 2 or 3 carbon-carbon parametric bonds. In some embodiments, alkynyl groups include ethynyl (-C≡CH), propargyl (or propynyl, such as -C≡CCH ₃ ), and the like. When the alkenyl or alkynyl moiety does not include a prefix indicating the number of carbon atoms, the alkenyl or alkynyl moiety or a portion thereof will have 12 or fewer main chain carbon atoms, or 8 or fewer main chain carbon atoms , 6 or fewer main chain carbon atoms or 4 or fewer main chain carbon atoms.

The term "alkynylene" refers to a straight or branched chain divalent hydrocarbon group containing at least one parametric bond and having the number of carbon atoms indicated in the prefix. Examples of such unsaturated alkyl groups include vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3- (1,4-pentadienyl), ethynyl, 1-propynyl and 3-propynyl, 3-butynyl and higher homologues and isomers.

"Alkoxy/alkoxyl" refers to -O-alkyl, where alkyl is as defined herein. As an example, "C ₁ -C ₆ alkoxy" refers to -OC ₁ -C ₆ alkyl, where alkyl is as defined herein. Although it should be understood that the substitution on the alkoxy group is attached at any available atom to produce a stable compound, the substitution of the alkoxy group should be such that O, S, or N (except where N is a heteroaryl ring atom) does not bind with Binding to the alkyl carbon of the alkoxy O. In addition, when an alkoxy group is described as a substituent of another part, the alkoxy oxygen does not bind to O, S or N (except where N is a heteroaryl ring atom) of another part or alkene or alkyne of another part. The carbon atoms of the hydrocarbon carbon are combined.

The terms "alkoxyalkyl" and "alkoxyalkylene" refer to an alkyl group substituted with an alkoxy group. As an example, "C ₁ -C ₆ alkoxy C ₁ -C ₆ alkyl" refers to C ₁ -C ₆ alkyl substituted by C ₁ -C ₆ alkoxy, wherein alkyl and alkoxy are such as As defined herein, "C ₁ -C ₃ alkoxy C ₁ -C ₃ alkylene" refers to C ₁ -C ₃ alkyl substituted by C ₁ -C ₃ alkoxy, wherein alkylene and The alkoxy group is as defined herein.

"Alkylsulfonyl" refers to the group -S(O) ₂ -alkyl, for example, C ₁ -C ₆ alkylsulfonyl is the group -S(O) ₂ -C ₁ -C ₆ alkyl. "Alkylsulfonyl alkylene" refers to the group alkylene -S(O) ₂ -alkyl, for example, C ₁ -C ₆ alkylsulfonyl C ₁ -C ₆ alkylene is -C ₁ -C ₆ alkylene-S(O) ₂ -C ₁ -C ₆ alkyl.

"Amino" or "amine" means the group -NH ₂ .

"Alkylamino" refers to -NH-alkyl, where alkyl is as defined herein. Exemplary alkylamino groups include CH ₃ NH-, ethylamino groups and the like. As an example, C ₁ -C ₆ alkylamino refers to -N(H)C ₁ -C ₆ alkyl.

The terms "aminoalkyl" and "aminoalkylene" refer to -alkylene-NH ₂ . As an example, C ₁ -C ₆ aminoalkyl refers to -C ₁ -C ₆ alkyl-NH ₂ . "Alkylamino alkylene" refers to -alkylene-NH-alkyl, for example, C ₁ -C ₆ alkylamino C ₁ -C ₆ alkylene is the group -C ₁ -C ₆ Alkylene-NH-C ₁ -C ₆ alkyl.

"Dialkylamino" refers to -N(alkyl)(alkyl), where each alkyl group is independently as defined herein. Exemplary dialkylamino groups include dimethylamino, diethylamino, ethylmethylamino, and the like. The di-C ₁ -C ₆ alkylamino group refers to -N(C ₁ -C ₆ alkyl) ₂ .

Unless otherwise specified, "cycloalkyl" or "carbocyclic" or "carbocyclic" by itself or as part of another substituent refers to a saturated or partially unsaturated, non-aromatic monocyclic or fused ring, such as a bicyclic ring Or tricyclic carbocyclic ring system, or cubane, which has the number of carbon atoms indicated in the prefix or, if not indicated, each ring has 3-6 or 4-6 or 5-6 ring members, such as ring For propyl, cyclopentyl, and cyclohexyl, one or two of the ring carbon atoms may be replaced by carbonyl groups as appropriate. In addition, the term cycloalkyl is intended to encompass ring systems fused to aromatic rings (such as aryl or heteroaryl), regardless of the point of attachment to the rest of the molecule. Cycloalkyl refers to a hydrocarbon ring having the indicated number of ring atoms (for example, C _3-6 cycloalkyl and 3-6 membered cycloalkyl both mean three to six ring carbon atoms). The term "cycloalkenyl" refers to a cycloalkyl group having at least one unit of unsaturation. The substituent of the cycloalkyl or cycloalkenyl group may be located at the point of attachment of the cycloalkyl or cycloalkenyl group to form a quaternary center.

"Cycloalkylalkyl" and "cycloalkylalkylene" refer to -(alkylene)-cycloalkyl, wherein the alkylene as defined herein has the indicated number of carbon atoms or if not indicated , Has six or fewer carbon atoms; and cycloalkyl as defined herein has the indicated number of carbon atoms or if not indicated, each ring has 3-10, or 3-8 , Or 3-6 ring members. As an example, a 4-6 membered cycloalkyl-C ₁ -C ₆ alkyl group refers to a cycloalkyl group having 4-6 carbon atoms attached to an alkylene chain having 1 to 6 carbon atoms, wherein the alkylene group The base chain is connected to the parent moiety. Other exemplary cycloalkylalkyl groups include, for example, cyclopropylmethylene, cyclobutylethylene, cyclobutylmethylene, and the like. "Cycloalkylalkynylene" refers to -(alkynylene)-cycloalkyl, for example C ₃ -C ₆ cycloalkyl C ₂ -C ₆ alkynylene is the group -(C ₂ -C ₆ alkynylene ) -C ₃ -C ₆ cycloalkyl. "C ₃ -C ₆ cycloalkylethynylene" is a group -C≡CC ₃ -C ₆ cycloalkyl.

"Cycloalkylalkoxy" refers to -(alkoxy)-cycloalkyl, in which an alkoxy group as defined herein has the indicated number of carbon atoms or, if not indicated, six or more Few carbon atoms; and cycloalkyl groups are as defined herein and have the indicated number of carbon atoms or if not indicated, each ring has 3-10, or 3-8, or 3-6 Ring members. As an example, a C ₃ -C ₆ cycloalkylalkoxy group refers to a cycloalkyl group having 3-6 ring carbon atoms connected to an alkoxy group having one to six carbon atoms, wherein the alkoxy chain is connected to the parent section. Other exemplary cycloalkylalkoxy groups include, for example, cyclopropylmethoxy, cyclobutylethoxy, cyclobutylmethoxy, and the like.

The term "cyano" refers to the group -CN. The term "C ₁ -C _{6 cyanoalkyl" refers to a C 1} -C ₆ alkyl group as defined herein substituted with 1, 2 or 3 cyano groups. "C ₁ -C ₆ cyanoalkylethynylene" is the group -C≡CC ₁ -C ₆ cyanoalkyl.

Unless otherwise specified, "aryl" by itself or as part of another substituent refers to a monocyclic, bicyclic or polycyclic polyunsaturated aromatic hydrocarbon radical containing 6 to 14 ring carbon atoms, which may be a single Rings or multiple rings (up to three rings) fused together or covalently connected. However, aryl does not cover or overlap with heteroaryl as defined below in any way. If one or more aryl rings are fused with a heteroaryl ring, the resulting ring system is a heteroaryl. Non-limiting examples of unsubstituted aryl groups include phenyl, 1-naphthyl, and 2-naphthyl. The term "aryl" refers to a divalent aryl group, where the aryl group is as defined herein.

"Arylalkyl" or "aralkyl" refers to -(alkylene)-aryl, where alkylene is as defined herein and has the indicated number of carbon atoms, or if not indicated, then It has six or fewer main chain carbon atoms, or four or fewer main chain carbon atoms; and the aryl group is as defined herein. Examples of arylalkyl groups include benzyl, phenethyl, 1-methylbenzyl, and the like. In another example, phenyl-C ₁ -C ₆ alkoxy refers to a phenyl group attached to a C ₁ -C ₆ alkoxy group, wherein the C ₁ -C ₆ alkoxy group is as defined herein and attached To the mother part.

The term "haloalkyl" refers to an alkyl group substituted with one to seven halogen atoms. Haloalkyl groups include monohaloalkyl groups or polyhaloalkyl groups. For example, the term "C ₁ -C ₆ haloalkyl" means to include trifluoromethyl, difluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl And its analogues. In addition, the term "haloalkylene" refers to an alkylene substituted with one to seven halogen atoms.

"Halogen" or "halo" refers to all halogens, namely chlorine (Cl), fluorine (F), bromine (Br) or iodine (I).

The term "haloalkoxy" refers to an alkoxy group substituted with one to seven halogen atoms. Haloalkoxy includes monohaloalkoxy or polyhaloalkoxy. For example, the term "C ₁ -C ₆ haloalkoxy" means to include trifluoromethoxy, difluoromethoxy, 2,2,2-trifluoroethoxy, 4-chlorobutoxy, 3-Bromopropoxy and its analogs.

"Heteroatom" means to include oxygen (O), nitrogen (N) and sulfur (S).

"Heteroaryl" refers to a monocyclic or bicyclic aromatic ring radical containing 5-9 ring atoms (also referred to as 5-9 membered heteroaryl in the present invention), including those containing 5 or 6 ring atoms Monocyclic aromatic ring radical (also called 5-6 membered heteroaryl in the present invention), which contains one or more, 1-4, 1-3 or 1-2 independently selected from the following Heteroatoms of the constituent group: O, S, and N. Any aromatic ring or ring system containing at least one heteroatom is a heteroaryl group regardless of the point of attachment (ie, via any fused ring). Heteroaryl is also intended to include oxidized S or N, such as sulfinyl, sulfonyl and tertiary ring nitrogen N-oxides. The carbon or nitrogen atom is the point of attachment of the heteroaryl ring structure, allowing stable compounds to be produced. Examples of heteroaryl groups include (but are not limited to) pyridyl, pyridazinyl, pyrazinyl, indolazinyl, benzo[b]thienyl, quinazolinyl, purinyl, indolyl, quinolinyl , Pyrimidinyl, pyrrolyl, pyrazolyl, oxazolyl, thiazolyl, thienyl, isoxazolyl, oxthiadiazolyl, isothiazolyl, tetrazolyl, imidazolyl, triazolyl, furanyl, Benzofuranyl, indolyl, triazinyl, quinolinyl, octolinyl, phthalazinyl, benzotriazinyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, benzo Isoxazolyl, isobenzofuranyl, isoindolyl, indolazinyl, benzotriazinyl, thienopyridyl, thienopyrimidinyl, pyrazolopyrimidinyl, imidazopyridine, benzothiazolyl , Benzothienyl, quinolyl, isoquinolyl, indazolyl, pteridyl and thiadiazolyl. The "nitrogen-containing heteroaryl group" refers to a heteroaryl group in which at least one ring heteroatom is N.

"Heteroarylalkyl" refers to -(alkylene)-heteroaryl, where alkylene is as defined herein and has the indicated number of carbon atoms, or if not indicated, six or Fewer main chain carbon atoms, or four or fewer main chain carbon atoms; and heteroaryl groups are as defined herein.

"Heterocycloalkyl" refers to a saturated or partially unsaturated non-aromatic group containing one to five heteroatoms selected from N, O, S (including S(O) and S(O) ₂ ) or P (including phosphine oxide) Group cycloalkyl, in which nitrogen, sulfur and phosphorus atoms are optionally oxidized, and nitrogen atoms are optionally quaternized, and the rest of the ring atoms are C, and one or two of the C atoms may optionally exist in the form of carbonyl groups. In addition, the term heterocycloalkyl is intended to encompass any ring or ring system containing at least one heteroatom that is not a heteroaryl group, regardless of the point of attachment to the rest of the molecule. Heterocycloalkyl groups include groups having a ring having an aromatic resonance structure with formal charge separation, such as N-methylpyridyl. Heterocycloalkyl groups may be substituted with one or two pendant oxy groups, and may include sulfonium and sulfide derivatives. The heterocycloalkyl group can be a monocyclic, fused bicyclic or fused polycyclic ring system with 3 to 12, 4 to 10, 5 to 10, or 5 to 6 ring atoms, of which one to five ring atoms are selected Heteroatoms from -N=, -N-, -O-, -S-, -S(O)- or -S(O) ₂ -, and in addition one or two of the ring atoms are optionally composed of -C( O)-group replacement. As an example, a 4-6 membered heterocycloalkyl group is a heterocycloalkyl group with 4-6 ring members having at least one heteroatom. The heterocycloalkyl group may also be a heterocycloalkyl ring fused with a cycloalkyl group. Non-limiting examples of heterocycloalkyl groups include pyrrolidinyl, piperidinyl, morpholinyl, pyridonyl and the like. The heterocycloalkyl group can be connected to the rest of the molecule via a ring carbon or a heteroatom. "Heterocycloalkenyl" refers to a heterocycloalkyl group having at least one unsaturated unit. Substituents of heterocycloalkyl or heterocycloalkenyl may be located at the point of attachment of heterocycloalkyl or heterocycloalkenyl, forming a quaternary center.

"Heterocycloalkylalkyl" or "heterocyclylalkyl" refers to -(alkylene)-heterocycloalkyl, wherein alkylene is as defined herein and has the indicated number of carbon atoms, Or if not indicated, it has six or fewer main chain carbon atoms, or four or fewer main chain carbon atoms; and the heterocycloalkyl group is as defined herein.

"Hydroxyl/hydroxy" refers to the group -OH. The term "hydroxyalkyl" or "hydroxyalkylene" refers to an alkyl group or alkylene group as defined herein which is substituted with 1 to 5 hydroxy groups, respectively.

The term "C ₁ -C _{6 haloalkoxy" refers to a C 1} -C ₆ alkoxy group as defined herein substituted with one or more halogen atoms.

The term "pendant oxy" refers to C(=0) or (O). In some embodiments, the two possible points of attachment on the carbon form pendant oxygen groups.

As used throughout the present invention, "optionally selected substituent" or "optionally substituted" means that the substitution on the compound may or may not exist, and the description includes examples in which substitutions exist and those in which substitutions do not exist. Instance. For example, the phrase " ^{replaced by 1-4 J 1} groups as appropriate" means that J ¹ groups are possible but not necessarily present. In the present invention, it is assumed that optional substitutions on the compound are performed in a manner that will result in a stable compound.

As used herein with respect to the compounds of the present invention, the term "synthesis" and similar terms mean chemical synthesis from one or more precursor materials.

As used herein, the term "composition" refers to a formulation suitable for administration to a desired animal for therapeutic purposes, which contains at least one pharmaceutically active compound and at least one pharmaceutically acceptable carrier or excipient.

The term "pharmaceutically acceptable" indicates that, taking into account the disease or condition to be treated and the respective route of administration, the indicated substance does not have the substance that would cause a very cautious medical practitioner to avoid administering the substance to the patient characteristic. For example, it is often necessary for such materials to be substantially sterile, for example for injectables.

"Pharmaceutically acceptable salt" refers to a salt that can be administered to a patient (such as a mammal) (for example, a salt that has acceptable mammalian safety for a given dose therapy). The pharmaceutically acceptable salt forms covered include (but are not limited to) single, double, ginseng, si, etc. The pharmaceutically acceptable salt is non-toxic in its dosage and concentration. The preparation of such salts can facilitate pharmacological use by changing the physical characteristics of the compound without preventing the compound from exerting its physiological effects. Applicable changes in physical properties include lowering the melting point to facilitate transmucosal administration and increasing solubility to facilitate the administration of higher concentrations of drugs. Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids, depending on the specific substituents found on the compounds described herein.

Pharmaceutically acceptable salts can be prepared by standard techniques. For example, the free base form of the compound can be dissolved in a suitable solvent (such as an aqueous solution or a water-alcohol solution containing a suitable acid) and then separated by evaporating the solution. In another example, a salt can be prepared by reacting a free base and an acid in an organic solvent.

When the compounds of the present invention contain relatively acidic functional groups, the neutral form of such compounds can be combined with pure or sufficient amounts of the required base (ie, primary, secondary, tertiary, etc.) in a suitable inert solvent. Grade, quaternary or cyclic amine; alkali metal hydroxide; alkaline earth metal hydroxide; or the like) to obtain an alkali addition salt. The required acid can be piperanosuronic acid (such as glucuronic acid or galacturonic acid), α-hydroxy acid (such as citric acid or tartaric acid), amino acid (such as aspartic acid or glutamine acid), aromatic Family acids (such as benzoic acid or cinnamic acid), sulfonic acids (such as p-toluenesulfonic acid or ethanesulfonic acid) or the like. In some embodiments, the salt may be derived from a pharmaceutically acceptable acid, such as acetic acid, trifluoroacetic acid, propionic acid, ascorbic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, tetrabutane Acrylic acid, glycolic acid, gluconic acid, glucuronic acid, glutamine acid, hippuric acid, hydrobromic acid, hydrochloric acid, isethionic acid, lactic acid, lactobionic acid, maleic acid, malic acid, malonic acid Acid, mandelic acid, oxalic acid, methanesulfonic acid, mucic acid, naphthalenesulfonic acid, nicotinic acid, nitric acid, pamoic acid, pantothenic acid, phosphoric acid, succinic acid, sulfuric acid, sulfamic acid, hydroiodic acid, carbonic acid, tartaric acid , P-toluenesulfonic acid, pyruvic acid, aspartic acid, benzoic acid, cinnamic acid, anthranilic acid, methanesulfonic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid, methylene pamoic acid (double Hydroxynaphthoic acid), ethanesulfonic acid, benzenesulfonic acid, 2-hydroxyethanesulfonic acid, p-aminobenzenesulfonic acid, stearic acid, cyclohexylamine sulfonic acid, cyclohexylaminosulfonic acid, quinic acid (quinic acid) acid), alginic acid, hydroxybutyric acid, galacturonic acid and galacturonic acid and their analogs.

Also includes salts of amino acids (such as arginine and its analogs), and salts of organic acids (such as glucuronic acid or galacturonic acid and their analogs) (see, for example, Berge, SM et al., "Pharmaceuticals Pharmaceutical Salts, J. Pharmaceutical Science, 1977, 66:1-19). Certain specific compounds of the present invention contain basic and acidic functional groups that allow the compound to be converted into a base addition salt or an acid addition salt.

The neutral form of the compound can be regenerated by contacting the salt with a base or acid and isolating the parent compound in a conventional manner. The parent form of the compound differs from various salt forms in certain physical properties, such as solubility in polar solvents, but for the purpose of the present invention, in other respects, the salt is equivalent to the parent form of the compound.

The pharmaceutically acceptable salts of different compounds may exist in the form of complexes. Examples of complexes include 8-chlorotheophylline complex (similar to, for example, dimenhydrinate: diphenhydramine 8-chlorotheophylline (1:1) complex; Dramamine) And various cyclodextrin inclusion complexes.

As used herein, the term "deuterated" alone or as part of a group means a substituted deuterium atom. As used herein, the term "deuterated analogue" alone or as part of a group means a substituted deuterium atom in place of hydrogen. The deuterated analog of the present invention may be a derivative completely or partially substituted with deuterium. In some embodiments, the deuterium-substituted derivatives of the present invention have fully or partially deuterium-substituted alkyl, aryl, or heteroaryl groups.

The present invention also covers isotopically-labeled compounds of the present invention, which are equivalent to the compounds listed in this article, but in fact one or more atoms have a different atomic mass or mass number from the atomic mass or mass number commonly found in nature. Atom replacement. All isotopic variations of the compounds of the present invention, whether radioactive or not, are intended to be included in the scope of the present invention. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as (but not limited to) ² H (deuterium, D), ³ H (tritium), ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ F, ³¹ P, ³² P, ³⁵ S, ³⁶ Cl and ¹²⁵ I. Unless otherwise specified, when a position is specifically designated as "H" or "hydrogen", the position should be understood as in its natural abundance isotopic composition or its isotopes (such as deuterium (D) or tritium (3H)) Has hydrogen in it. Certain isotopically-labeled compounds of the present invention (for example, ³ H or ¹⁴ C-labeled compounds) are suitable for compound and/or substrate tissue distribution analysis. Tritiated (ie, ³ H) and carbon-14 (ie, ¹⁴ C) and fluorine-18 ( ¹⁸ F) isotopes are suitable for their ease of preparation and detectability. In addition, substitution with heavier isotopes (such as deuterium (ie, ² H)) can provide certain therapeutic advantages resulting from greater metabolic stability (for example, extended in vivo half-life or reduced dosage requirements), and Therefore, it may be better in some cases. The isotopically-labeled compounds of the present invention can generally be prepared by replacing the non-isotopically-labeled reagents with isotopically-labeled reagents according to procedures similar to those described in the following procedures and examples.

"Prodrug" means any compound that releases the active parent drug according to Formula I in vivo when such prodrug is administered to an individual. The prodrug of the compound of formula I is prepared by modifying the functional group of the compound of formula I in a conventional operation or in vivo, so that the modified substance can be cleaved in vivo to release the parent compound. A prodrug can be converted from a prodrug form to an active form in a single step, or can have one or more intermediate forms, which can be active or inactive by itself. Some prodrugs are activated enzymatically to obtain active compounds, or compounds that generate active compounds during further chemical reactions. Prodrugs include compounds of formula I that satisfy the following conditions: the hydroxyl, amine, carboxyl or sulfhydryl group in the compound of formula I is bonded to any group that can be cleaved in vivo to regenerate free hydroxyl, amine or sulfhydryl groups, respectively. Examples of prodrugs include, but are not limited to, esters of hydroxyl functional groups in compounds of formula I (e.g. acetate, formate and benzoate derivatives), amides, guanidines, carbamates (e.g. N,N-dimethylaminocarbonyl) and its analogues. Other examples of prodrugs include, but are not limited to, carbonate, urea, solvate, or hydrate of the active compound. The preparation, selection and use of prodrugs are discussed in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems", 14th of "ACS Symposium Series" Volume; "Design of Prodrugs", edited by H. Bundgaard, Elsevier, 1985; and "Bioreversible Carriers in Drug Design", edited by Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, each of which is incorporated herein by reference in its entirety.

As described in "The Practice of Medicinal Chemistry", Chapters 31-32 (Wermuth, Academic Press, San Diego, CA, 2001), prodrugs can be conceptually divided into two non-exclusive categories, biological Precursor prodrugs and carrier prodrugs. Generally, a bioprecursor prodrug is a compound that contains one or more protective groups and is converted into an active form by metabolism or solvolysis, which is inactive or less active than the corresponding active pharmaceutical compound. The active drug form and any released metabolites should have acceptable low toxicity. Generally, the formation of active pharmaceutical compounds involves one of the following types of metabolic processes or reactions:

(1) Oxidation reaction: The oxidation reaction is (but not limited to) the reactions exemplified, such as the oxidation of alcohols, carbonyl groups and acid functional groups; hydroxylation of aliphatic carbons; hydroxylation of alicyclic carbon atoms; aromatic carbon atoms Oxidation of carbon-carbon double bond; Oxidation of nitrogen-containing functional groups; Oxidation of silicon, phosphorus, arsenic and sulfur; Oxidative N-dealkylation; Oxidative O- and S-dealkylation; Oxidative deamine化; and other oxidation reactions.

(2) Reduction reaction: The reduction reaction is (but not limited to) the exemplified reactions, such as the reduction of carbonyl functional groups; the reduction of alcohol functional groups and carbon-carbon double bonds; the reduction of nitrogen-containing functional groups; and other reduction reactions.

(3) Reactions without change in oxidation state: Reactions without change in oxidation state are (but not limited to) the exemplified reactions, such as the hydrolysis of esters and ethers; the hydrolysis of carbon-nitrogen single bonds; the hydrolysis of non-aromatic heterocycles Splitting; hydration and dehydration at multiple bonds; new atomic bonds produced by dehydration reactions; hydrolytic dehalogenation; removal of hydrogen halide molecules; and other such reactions.

A carrier prodrug is, for example, a drug compound containing a delivery moiety that improves absorption and/or local delivery to the site of action. For such carrier prodrugs, it is desirable that the bond between the drug moiety and the delivery moiety is a covalent bond, the prodrug is inactive or less active than the drug compound, and the prodrug and any released delivery moiety are capable of Acceptance is non-toxic. For the drug before the delivery part is intended to enhance absorption, the release of the delivery part should generally be rapid. In other cases, it is necessary to use parts that provide slow release, such as certain polymers or other parts, such as cyclodextrin (see, for example, Cheng et al., US Patent Publication No. 2004/0077595, which is incorporated by reference In this article). Such carrier prodrugs usually facilitate oral administration of the drug. For example, carrier prodrugs can be used to improve one or more of the following properties: increased lipophilicity, increased duration of pharmacological effects, increased site specificity, decreased toxicity and adverse reactions, and/or drug formulation Improvement of substances (such as stability, water solubility, inhibition of undesirable sensory or biochemical properties). For example, the lipophilicity can be improved by esterification of a hydroxyl group with a lipophilic carboxylic acid or esterification of a carboxylic acid group with an alcohol (for example, aliphatic alcohol).

The term "carrier" also means to include microspheres, liposomes, micelles, nanoparticles (naturally equipped nanocarriers, such as extracellular bodies) and the like. It is known that exosome can be a highly effective drug carrier, and there are many methods for loading drugs into exosome, including "J Control Release.", December 10, 2015; 219: 396- The content of the technology described in 405 is incorporated by reference in its entirety.

Metabolites, such as active metabolites, overlap with prodrugs (eg bioprecursor prodrugs) as described above. Therefore, such metabolites are pharmacologically active compounds or compounds that are further metabolized into pharmacologically active compounds (which are derivatives produced by metabolic processes in the body of the individual). Among them, active metabolites are such pharmacologically active derivative compounds. For prodrugs, the prodrug compound is usually inactive or less active compared to the metabolite. For active metabolites, the parent compound may be the active compound or may be an inactive prodrug.

Conventional techniques known in the art can be used to identify prodrugs and active metabolites. See, for example, Bertolini et al., 1997, "J. Med. Chem.", 40:2011-2016; Shan et al., 1997, "J Pharm Sci", 86(7): 756-757; Bagshawe, 1995, "Drug Dev. Res.", 34:220-230.

"Tautomer" means a compound produced by the migration of a proton from one atom of a molecule to another atom. See Jerry March, "Advanced Organic Chemistry: Reactions, Mechanisms and Structures", Fourth Edition, John Wiley & Sons, pp. 69-74 (1992). Tautomers also refer to one of two or more structural isomers that exists in a balanced manner and is easily converted from one isomeric form to another isomeric form. Examples include keto-enol tautomers, such as acetone/propene-2-ol, imine-enamine tautomers and their analogs; ring-chain tautomers, such as glucose/2,3,4 ,5,6-pentahydroxy-hexanal and its analogues; tautomeric forms of heteroaryl groups containing -N=C(H)-NH- ring atoms, such as pyrazole, imidazole, benzimidazole, tri Azole and tetrazole. When the compound contains, for example, a ketone or oxime group or an aromatic moiety, there may be tautomeric isomerism ("tautomerism"). The compounds described herein may have one or more tautomers and therefore include various isomers. Those skilled in the art will recognize that other tautomeric ring atom arrangements may exist. All such isomeric forms of these compounds are expressly included in the present invention.

"Isomer" means a compound that has the same molecular formula but differs in the bonding nature or sequence of atoms or the arrangement of atoms in space. Isomers that differ in the arrangement of atoms in space are called "stereoisomers". "Stereoisomers" refer to compounds that exist in different stereoisomeric forms, for example, if they have one or more asymmetric centers or have asymmetrically substituted double bonds and therefore can be individual stereoisomers or mixtures The form is produced. Stereoisomers include enantiomers and diastereomers. Stereoisomers that are not mirror images of each other are called "diastereomers" and stereoisomers that are non-superimposable mirror images of each other are called "enantiomers". When the compound has an asymmetric center, for example, atoms bonded to four different groups, such as carbon, a pair of enantiomeric systems is possible. Enantiomers can be characterized by the absolute configuration of their asymmetric centers and described according to the R-sequencing rules and S-sequencing rules of Cahn and Prelog, or described and specified by the rotation of molecules around the plane of polarized light It is right-handed or left-handed (that is, (+) or (-)-isomer, respectively). Opposite compounds may exist in the form of individual enantiomers or in the form of mixtures thereof. A mixture containing equal proportions of enantiomers is called a "racemic mixture". As another example, stereoisomers include geometric isomers such as the cis or trans orientation of substituents on adjacent carbons of a double bond. Unless otherwise indicated, the description is intended to include individual stereoisomers as well as mixtures. The method for determining the stereochemistry and separation of stereoisomers with different counterparts in one or more stereogenic centers is well-known in the art (see "Advanced Organic Chemistry", page 6 Edition, J. March, John Wiley and Sons, New York, 2007, Chapter 4).

"Hydrate" refers to a complex formed by combining water molecules and solute molecules or ions. "Solvate" refers to a complex formed by combining solvent molecules and solute molecules or ions. The solvent can be an organic compound, an inorganic compound, or a mixture of the two. Solvate is meant to include hydrates. Some examples of solvents include, but are not limited to, methanol, N,N-dimethylformamide, tetrahydrofuran, dimethylsulfoxide, and water. Generally, the fusion form is equivalent to the non-fusion form and is encompassed within the scope of the present invention.

In the context of the use, testing, or screening of compounds that are or can be modulators, the term "contact" means bringing the compound sufficiently close to a specific molecule, complex, cell, tissue, organism, or other specified substance that potentially binds to the interaction And/or chemical reactions can be carried out between the compound and other designated substances.

"Analysis" means the generation of experimental conditions and the collection of data about specific results of exposure to specific experimental conditions. For example, enzymes can be analyzed based on their ability to act on detectable substrates. Compounds can be analyzed based on their ability to bind to specific target molecules or molecules.

As used herein, the terms "ligand" and "modulator" are equivalently used to refer to altering (ie, increasing or decreasing) the activity of a target biomolecule (for example, an enzyme, such as the enzyme described herein) The compound. Generally, the ligand or modulator will be a small molecule, where "small molecule" refers to having 1500 Dalton (Dalton) or lower, 1000 Dalton or lower, 800 Dalton or lower, or 600 Dalton. Compounds with molecular weights of ton or lower. Therefore, "improved ligands" are ligands that have better pharmacological and/or pharmacokinetic properties than the reference compound, where "better" can be used in specific biological systems or related fields of therapeutic use Defined by those who are familiar with this technology.

The term "binding" used with regard to the interaction between the target and the potential binding compound indicates that the potential binding compound binds to the target to a statistically significant degree compared to the general binding to the protein (ie, non-specific binding). Therefore, the term "binding compound" refers to a compound that has a statistically significant binding to the target molecule. In some embodiments, the binding compound is at 10 mM or lower, 1,000 µM or lower, 100 µM or lower, 10 µM or lower, 1 µM or lower, 1,000 nM or lower, 100 nM or lower , 10 nM or lower or 1 nM or lower dissociation constant (K _D ) interacts with the specified target. In the case of a compound that binds to the target, the terms "greater affinity" and "selectivity" indicate that the compound binds more tightly than the reference compound or the same compound in the reference conditions, that is, dissociates at a lower level constant. In some embodiments, the greater affinity is at least 2, 3, 4, 5, 8, 10, 50, 100, 200, 400, 500, 1000, or 10,000 times greater affinity.

The term "modulate/modulation" and similar terms refer to the ability of a compound to increase or decrease the function and/or performance of a target (such as EP300 or CBP), where such functions may include transcriptional regulatory activity and/or binding. The adjustment can be performed in vitro or in vivo. As described herein, modulation includes direct or indirect inhibition, antagonism, partial antagonism, activation, agonist or partial agonism of functions or features associated with EP300 or CBP, and/or direct or indirect performance of EP300 or CBP Up or down. In another embodiment, the adjustment is direct. Inhibitors or antagonists are, for example, compounds that bind to, partially or completely block stimulation, decrease, prevent, inhibit, delay activation, inactivation, desensitization or down-regulation of signal transduction. An activator or agonist is, for example, a compound that binds to, stimulates, increases, opens, activates, promotes, enhances activation, activates, sensitizes, or upregulates signal transduction.

As used herein, the terms "treat/treating", "therapy/therapies" and similar terms refer to effectively preventing, alleviating or ameliorating one or more symptoms of a disease or condition (ie, Indications) and/or administer the material in an amount that prolongs the survival of the individual being treated, for example, any one or more of the compounds as described herein.

As used herein, the term "prevent (prevent/preventing/prevention)" and its grammatical variants refer to methods used to achieve the following goals: partially or completely delay or hinder a disease, disorder or condition and/or one or one of them The onset or recurrence of various concomitant symptoms, or prevents the individual from suffering or re-suffering a disease or condition, or reduces the risk of the individual suffering from or developing a disease or condition or one or more of its concomitant symptoms.

As used herein, the terms "individual", "animal individual" and their analogs refer to living organisms, including (but not limited to) humans and non-human vertebrates, such as any mammals such as humans and other primates Animals, sports animals and animals of commercial significance, such as cows, horses, sheep or pigs, rodents or pets, such as dogs and cats.

"Unit dosage form" refers to a composition intended for a single administration to treat an individual suffering from a disease or medical condition. Each unit dosage form typically contains each of the active ingredients of the present invention plus pharmaceutically acceptable excipients. Examples of unit dosage forms are individual lozenges, individual capsules, bulk powders, liquid solutions, ointments, creams, eye drops, suppositories, emulsions or suspensions. Treatment of diseases or conditions may require periodic administration of unit dosage forms, for example: a unit dosage form twice or more a day, once with each meal, once every four hours or other intervals, or only once a day. The expression "oral unit dosage form" indicates a unit dosage form designed for oral administration.

The term "administration" refers to oral administration, administration in the form of suppositories, local contact, intravenous, intraperitoneal, intramuscular, intralesional, intranasal or subcutaneous administration or implantation of slow release devices, such as micro-osmotic Pump. Administration is by any route, including parenteral and transmucosal (eg, intrabuccal, sublingual, transpalatal, transgingival, transnasal, transvaginal, transrectal or transdermal). Parenteral administration includes, for example, intravenous, intramuscular, intraarteriole, intradermal, subcutaneous, intraperitoneal, intraperitoneal, and intracranial. Other modes of delivery include (but are not limited to) the use of liposome formulations, intravenous infusion, transdermal patches, etc.

As used herein, the term "therapeutically effective" or "effective amount" indicates that when administered, the compound or material or the amount of the compound or material is sufficient or effective to prevent, alleviate or ameliorate the disease, disorder or medical condition being treated One or more symptoms, and/or prolong the survival period of the individual being treated. The therapeutically effective amount will vary depending on the compound, disease, disorder or condition and its severity, as well as the age, weight, etc. of the mammal being treated. Generally speaking, it is instructed that satisfactory results for an individual are obtained at a daily dose of about 0.1 to about 10 g/kg of the individual's body weight. In some embodiments, the daily dose is about 0.10 to 10.0 mg/kg body weight, about 1.0 to 3.0 mg/kg body weight, about 3 to 10 mg/kg body weight, about 3 to 150 mg/kg body weight, about 3 to 100 mg. /kg body weight, about 10 to 100 mg/kg body weight, about 10 to 150 mg/kg body weight, or about 150 to 1000 mg/kg body weight. The dosage can be conveniently administered, for example, in divided doses up to four times a day or in a sustained release form.

The ability of the compound to inhibit the function of EP300 or CBP can be demonstrated in biochemical analysis (such as binding analysis) or cell-based analysis.

As used herein, the term "EP300 or CBP-mediated disease or condition" refers to a disease or condition in which the biological functions of EP300, CBP or EP300 and CBP affect the development and/or course of the disease or condition and/or in which EP300 , CBP or the regulation of both EP300 and CBP can change the development, course and/or symptoms of the disease or condition. EP300 or CBP-mediated diseases or conditions include diseases or conditions in which EP300 inhibition, CBP inhibition, or both EP300 and CBP inhibition can provide therapeutic benefits, for example, EP300 or CBP inhibitors (including the compounds described herein) ) The treatment performed can provide therapeutic benefits to individuals suffering from or at risk of suffering from the disease or condition. EP300 or CBP-mediated diseases or conditions are intended to include cancers with loss of functional mutations of CBP or EP300, or cancers in which EP300 or CBP activation is present. EP300 or CBP-mediated diseases or conditions are also intended to include cancers that exhibit androgen receptors.

The term "EP300-mediated diseases or disorders" includes diseases associated with or related to EP300 activity (for example, EP300 overactivity), and conditions that accompany these diseases. The term "excessive activity of EP300" refers to: 1) EP300 expression in cells that do not normally express EP300; 2) EP300 expression that causes an increase in undesirable cell proliferation; or 3) mutations that cause constitutive activation of EP300. EP300-mediated diseases or conditions will include tumors with CBP inactivating mutations (also known as synthetic lethality). Examples of EP300-mediated diseases or conditions include conditions caused by an abnormally large amount of EP300 activity. EP300-mediated diseases or conditions are intended to include cancers with loss of functional mutations in CBP, or cancers with activation of EP300 in them. EP300-mediated diseases or conditions are also intended to include cancers that exhibit androgen receptors. It is known that the excessive activity of EP300 is related to the pathogenesis of a variety of diseases, including proliferative and non-proliferative disorders, including neoplastic disorders and cancer, inflammatory disorders, cognitive disorders, and neurodegenerative diseases.

The term "CBP-mediated diseases or disorders" includes diseases associated with or related to CBP activity (for example, CBP overactivity), and conditions that accompany these diseases. The term "excessive activity of CBP" refers to: 1) CBP expression in cells that do not normally express CBP; 2) CBP expression that causes an increase in undesirable cell proliferation; or 3) mutations that cause constitutive activation of CBP. Examples of CBP-mediated diseases or disorders include disorders caused by abnormally large amounts of CBP activity. CBP-mediated diseases or conditions are intended to include cancers with loss of functional mutations in EP300, or cancers in which CBP activation is present. CBP-mediated diseases or conditions are also intended to include cancers that exhibit androgen receptors. It is known that the excessive activity of CBP is related to the pathogenesis of various diseases, including proliferative and non-proliferative disorders, including neoplastic disorders and cancer, inflammatory disorders, cognitive disorders, and neurodegenerative diseases.

Also, in the case of a compound that binds to a biomolecular target, the term "greater specificity" indicates that the compound binds to a greater degree than another biomolecule or multiple biomolecules that can exist under relevant binding conditions In a designated target, where the binding to such other biomolecules produces a biological activity that is different from the binding to the designated target. Typically, specificity relates to a limited set of other biomolecules, such as in the case of EP300, CBP, or even other epigenetic targets. In certain embodiments, the greater specificity is at least 2, 3, 4, 5, 8, 10, 50, 100, 200, 400, 500, or 1000 times greater specificity.

As used herein with regard to binding compounds or ligands, the term "specific to EP300" and terms with similar meanings mean that a specific compound is statistically compared to other epigenetic targets that may be present in a specific sample. To a greater extent combined with EP300. In addition, when indicating biological activities other than binding, the term "specific to EP300" indicates that compared with other enzymes, a specific compound has greater biological effects associated with binding to EP300, such as inhibition of enzyme activity. Specificity also targets other biomolecules that may be present in a specific sample (not limited to EP300).

As used herein with regard to binding compounds or ligands, the term "specific to CBP" and terms with similar meanings mean that a specific compound is statistically compared to other epigenetic targets that may be present in a specific sample. To a greater extent is bound to CBP. In addition, when indicating biological activity other than binding, the term "specific to CBP" indicates that compared with other enzymes, a specific compound has a greater biological effect associated with binding to CBP, such as inhibition of enzyme activity. Specificity also targets other biomolecules that may be present in a specific sample (not limited to CBP).

The term "first-line cancer therapy" refers to a therapy that is administered to an individual as an initial regimen to reduce the number of cancer cells. First-line therapy is also called induction therapy, initial therapy and initial treatment. The first-line therapy can be a combination of one or more agents administered with it. An overview of currently accepted methods for the first-line treatment of certain diseases can be found in the NCI guidelines for such diseases.

The term "second-line cancer therapy" refers to individuals who do not respond to first-line therapy (ie, are usually administered first-line therapy) or who have recurrence of cancer after remission are administered cancer therapy. In certain embodiments, the second-line therapy that can be administered includes repeated initial successful cancer therapy, which can be any of the treatments described under "First-line Cancer Therapy." An overview of currently accepted methods for second-line treatment of certain diseases is described in the NCI guidelines for such diseases.

The term "refractory" refers to a situation in which an individual does not respond or is otherwise resistant to cancer therapy or treatment. Cancer therapy can be first-line, second-line, or any subsequent administration. In certain embodiments, refractory refers to a condition in which the individual fails to achieve complete remission after two induction attempts. An individual may be refractory due to the inherent resistance of cancer cells to a particular therapy, or an individual may be refractory due to acquired resistance developed during or after the course of a particular therapy.

In addition, the abbreviations used in this article have the following respective meanings: °C Celsius Ac Acetyl BOC Tertiary butyloxycarbonyl DBU 1,8-diazabicyclo[5.4.0]undec-7-ene DCM Dichloromethane DEAE Diethylaminoethyl DMAP Dimethylaminopyridine DMEM Dulbecco's Modified Eagle's Medium DME Dimethoxyethane DMF Dimethylformamide DMSO Diabetes ESI Electrospray ionization FBS Fetal Bovine Serum HPLC High performance liquid chromatography LCMS Liquid Chromatography Mass Spectrometry [M+H+]+ or (MH)+ Mass spectrum peak hydrogenation [MH-]-or (MH)- Mass peak minus hydrogen mCPBA M-chloroperoxybenzoic acid Me methyl MeOH Methanol MS Mass spectrometry PBS Phosphate buffer solution RT Room temperature S-Phos 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl TBAF Tetrabutylammonium fluoride TLC Thin layer chromatography THF Tetrahydrofuran n-Bu N-butyl N normal IC ₅₀ Half maximum (50%) inhibitory concentration RP Reverse phase X-Phos 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl II. Compound

或其醫藥學上可接受之鹽、溶劑合物、互變異構體、立體異構體或氘化類似物，其中： A¹ 為R⁶ ，A² 為R⁷ ，A³ 為-L-R¹ ，A⁴ 為R⁵ ，X¹ 為CH，X² 為C且X³ 為N；或 A¹ 為R⁶ ，A² 為R⁷ ，A³ 為-L-R¹ ，A⁴ 為R⁵ ，X¹ 為CH，X² 為C且X³ 為CH；或 A¹ 為R⁶ ，A² 不存在，A³ 為-L-R¹ ，A⁴ 為R⁵ ，X¹ 為CH，X² 為N且X³ 為CH；或 A¹ 為R⁷ ，A² 為R⁶ ，A³ 為-L-R¹ ，A⁴ 為R⁵ ，X¹ 為N，X² 為C且X³ 為CH；或 A¹ 為R⁷ ，A² 為R⁶ ，A³ 為R⁵ ，A⁴ 為-L-R¹ ，X¹ 為N，X² 為C且X³ 為CH； L為一鍵、-CH₂ -CH₂ -、-(CH₂ )_1-2 -CH=CH-(CH₂ )_0-1 -、-CR² R³ -、-C(O)-或-S(O)₂ -； L² 為一鍵或-C(R¹³ )₂ -； R¹ 為苯基、5-9員雜芳基、C₃ -C₆ 環烷基、C₅ -C₆ 環烯基、 4-9員雜環烷基或5-6員雜環烯基，其中R¹ 視情況經1個G¹ 基團及1-3個G² 基團取代； R² 為H、C₁ -C₆ 烷基或OH； R³ 為H、C₁ -C₆ 烷基、C₁ -C₆ 氰基烷基、C₁ -C₆ 鹵烷基、C₃ -C₆ 環烷基或5-6員雜芳基； R⁴ 為H、OH、C₁ -C₆ 烷基或C₁ -C₆ 鹵烷基； 當連接至碳時，R⁵ 為4-6員環烷基、5-6員環烯基、苯基、5-9員雜芳基、5-6員雜環烷基、4-6員環烷基-C₁ -C₆ 烷基、

或

，其中4-6員環烷基、5-6員環烯基、苯基、5-9員雜芳基或4-6員環烷基-C₁ -C₆ 烷基各自視情況經一個L² -J¹ 基團及0-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子； 或當連接至氮之時，R⁵ 為4-6員環烷基、5-6員環烯基、苯基、5-9員雜芳基或4-6員環烷基-C₁ -C₆ 烷基，其中4-6員環烷基、5-6員環烯基、苯基、5-9員雜芳基或4-6員環烷基-C₁ -C₆ 烷基各自視情況經1個-L² -J¹ 基團及1-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子； R⁶ 為含有至少一個氮原子之五員雜芳基，其中5員雜芳基視情況經0-2個R⁸ 基團取代； R⁷ 為H、鹵基或C₁ -C₆ 烷基； R⁸ 為C₁ -C₆ 烷基或C₁ -C₃ 烷氧基C₁ -C₃ 伸烷基； 各R¹⁰ 獨立地為H、C₁ -C₆ 烷基、C₁ -C₆ 鹵烷基或環丙基； 各R¹¹ 獨立地為、C₁ -C₆ 烷基或C₁ -C₆ 鹵烷基，或兩個R¹¹ 基團與所述兩個R¹¹ 基團所連接之碳原子共同連接以形成環丙基； 各R¹² 獨立地為H、C₁ -C₆ 烷基、C₁ -C₆ 羥基烷基或C₁ -C₆ 鹵烷基； 各R¹³ 獨立地為H、CH₃ 或F，或各R¹³ 與其所連接之碳原子共同形成C₃ -C₆ 環烷基； R¹⁴ 為H、C₁ -C₆ 烷基或C₁ -C₃ 烷氧基C₁ -C₃ 伸烷基； G¹ 為氰基、C₂ -C₆ 烯基、C₁ -C₆ 氰基烷基、C₁ -C₆ 氰基烷基伸乙炔基、C₂ -C₆ 烯基C₁ -C₆ 伸烷基、C₁ -C₆ 烷基磺醯基、C₁ -C₆ 烷基磺醯基C₁ -C₆ 伸烷基、-N(R¹⁰ )₂ 、二-C₁ -C₆ 烷基胺基C₁ -C₆ 伸烷基、C₁ -C₆ 烷基胺基C₁ -C₆ 伸烷基、胺基C₁ -C₆ 伸烷基、-C(O)- C₁ -C₆ 烷基、-C(O)-C₁ -C₆ 羥基烷基、-C(O)-C₁ -C₆ 鹵烷基、-C(O)OR¹² 、-C₁ -C₃ 伸烷基-C(O)OR¹² 、-C(O)-N(H)-C₃ -C₆ 環烷基、C₃ -C₆ 環烷基、C₃ -C₆ 環烷基C₁ -C₆ 伸烷基、C₃ -C₆ 環烷基C₂ -C₆ 伸炔基、4-6員雜環烷基、-C(O)-N(R¹⁰ )₂ 、-C₁ -C₆ 伸烷基-C(O)-N(R¹⁰ )₂ 或苯基C₁ -C₆ 烷氧基，限制條件為當G¹ 連接至氮原子時，G¹ 不為氰基； 各G² 獨立地為鹵基、C₁ -C₆ 烷基、C₁ -C₆ 鹵烷基、C₁ -C₆ 烷氧基、C₁ -C₆ 鹵烷氧基、OH、側氧基、C₁ -C₆ 羥基烷基，限制條件為當G² 連接至氮原子時，G² 不為鹵基、C₁ -C₆ 烷氧基、C₁ -C₆ 鹵烷氧基或OH； J¹ 為-C(R¹¹ )₂ -C(O)OH、-C(O)OH、-C(O)O-C₁ -C₆ 烷基、CH₂ -C(O)O-C₁ -C₆ 烷基、-C(O)N(R¹⁰ )₂ 、-C(O)N(H)-CN、-C(O)N(H)OH、-C(O)N(H)-SO₂ -C₁ -C₆ 烷基、-N(H)-SO₂ -C₁ -C₆ 烷基、C₁ -C₆ 烷基磺醯基、四唑基或-S(O)₂ -N(R¹⁰ )₂ ；及 各J² 獨立地為4-6員雜環烷基、-O-(4-6員雜環烷基)、-O-C₃ -C₆ 環烷基、C₃ -C₆ 環烷基烷氧基、苯基C₁ -C₆ 烷氧基、C₁ -C₆ 烷基、C₁ -C₆ 烷氧基、鹵基、C₁ -C₆ 鹵烷基、C₁ -C₆ 鹵烷氧基、OH、C₁ -C₆ 羥基烷基、CN、C₁ -C₆ 氰基烷基、C₂ -C₆ 炔基、C₃ -C₆ 環烷基伸乙炔基、C₃ -C₆ 環烷基、4-6員雜環烷基、NO₂ 或-N(R¹⁰ )₂ ，限制條件為當J² 連接至氮時，J² 不為-O-(4-6員雜環烷基)、-O-C₃ -C₆ 環烷基、C₃ -C₆ 環烷基烷氧基、苯基C₁ -C₆ 烷氧基、C₁ -C₆ 烷氧基、鹵基、C₁ -C₆ 鹵烷氧基、OH、CN、C₂ -C₆ 炔基、C₃ -C₆ 環烷基伸乙炔基或-N(R¹⁰ )₂ 。 Example 1 of the present invention relates to the compound of I: 1. The compound of formula I:

Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog thereof, wherein: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is CH, X ² is C and X ³ is N; or A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is CH, X ² is C and X ³ is CH; or A ¹ is R ⁶ , A ^{2 is} not present, A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is CH, X ² is N and X ³ is CH; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, X ² is C and X ³ is CH; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, X ² is C and X ³ is CH; L is a bond, -CH ₂ -CH ₂ -, -(CH ₂ ) _1-2 -CH=CH-(CH ₂ ) _0-1 -, -CR ² R ³ -, -C(O)- or -S(O) ₂ -; L ² is a bond or -C( R ¹³ ) ₂ -; R ¹ is phenyl, 5-9 membered heteroaryl, C ₃ -C ₆ cycloalkyl, C ₅ -C ₆ cycloalkenyl, 4-9 membered heterocycloalkyl or 5-6 Membered heterocycloalkenyl, where R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups; R ² is H, C ₁ -C ₆ alkyl or OH; R ³ is H, C ₁ -C ₆ alkyl, C ₁ -C ₆ cyanoalkyl, C ₁ -C ₆ haloalkyl, C ₃ -C ₆ cycloalkyl or 5-6 membered heteroaryl; R ⁴ is H, OH, C ₁ -C ₆ alkyl or C ₁ -C ₆ haloalkyl; when connected to carbon, R ⁵ is 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl, 5-9 membered hetero Aryl, 5-6 membered heterocycloalkyl, 4-6 membered cycloalkyl-C ₁ -C ₆ alkyl,

or

, Wherein 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl, 5-9 membered heteroaryl, or 4-6 membered cycloalkyl-C ₁ -C ₆ alkyl group is optionally connected to a L ² -J ¹ group and 0-4 J ² groups are substituted, the restriction is that J ^{1 is} directly bonded to a carbon atom; or when connected to nitrogen, R ⁵ is 4-6 membered cycloalkyl, 5- 6-membered cycloalkenyl, phenyl, 5-9-membered heteroaryl or 4-6-membered cycloalkyl-C ₁ -C ₆ alkyl, wherein 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, Phenyl, 5-9 membered heteroaryl or 4-6 membered cycloalkyl-C ₁ -C ₆ alkyl are each ^{substituted with 1 -L 2} -J ¹ group and 1-4 J ² groups as appropriate , The restriction condition is that J ^{1 is} directly bonded to a carbon atom; R ⁶ is a five-membered heteroaryl group containing at least one nitrogen atom, wherein the five-membered heteroaryl group is optionally ^{substituted by 0-2 R 8} groups; R ⁷ is H, halo or C ₁ -C ₆ alkyl; R ⁸ is C ₁ -C ₆ alkyl or C ₁ -C ₃ alkoxy C ₁ -C ₃ alkylene; each R ^{10 is} independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl or cyclopropyl; each R ^{11 is} independently, C ₁ -C ₆ alkyl or C ₁ -C ₆ haloalkyl, or two R ¹¹ groups The group and the ^{carbon atom to which the two R 11} groups are connected are jointly connected to form a cyclopropyl group; each R ^{12 is} independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ hydroxyalkyl, or C ₁ -C ₆ haloalkyl; each R ^{13 is} independently H, CH ₃ or F, or each R ¹³ and the carbon atom to which it is connected together form a C ₃ -C ₆ cycloalkyl group; R ¹⁴ is H, C ₁ -C ₆ alkyl or C ₁ -C ₃ alkoxy C ₁ -C ₃ alkylene; G ¹ is cyano, C ₂ -C ₆ alkenyl, C ₁ -C ₆ cyanoalkyl, C ₁ -C ₆ Cyanoalkylethynylene, C ₂ -C ₆ alkenyl C ₁ -C ₆ alkylene, C ₁ -C ₆ alkylsulfonyl, C ₁ -C ₆ alkylsulfonyl C ₁ -C ₆ Alkyl group, -N(R ¹⁰ ) ₂ , di-C ₁ -C ₆ alkylamino group C ₁ -C ₆ alkylene group, C ₁ -C ₆ alkylamino group C ₁ -C ₆ alkylene group, amine C ₁ -C ₆ alkylene group, -C(O)-C ₁ -C ₆ alkyl group, -C(O)-C ₁ -C ₆ hydroxyalkyl group, -C(O)-C ₁ -C ₆ Haloalkyl, -C(O)OR ¹² , -C ₁ -C ₃ alkylene-C(O)OR ¹² , -C(O)-N(H)-C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₆ alkylene, C ₃ -C ₆ cycloalkyl, C ₂ -C ₆ alkynylene, 4-6 membered heterocycloalkyl , -C(O)-N(R ¹⁰ ) ₂ , -C ₁ -C ₆ alkylene-C(O)-N(R ¹⁰ ) ₂ or phenyl C ₁ -C ₆ alkoxy, with the restriction that when G ^{1 is} connected to a nitrogen atom, G ^{1 is} not a cyano group; each G ² Independently halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy, OH, pendant oxy, C ₁ -C ₆ hydroxyalkyl, the restriction is that when G ^{2 is} connected to a nitrogen atom, G ^{2 is} not a halo, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy or OH; J ¹ is -C(R ¹¹ ) ₂ -C(O)OH, -C(O)OH, -C(O)OC ₁ -C ₆ alkyl, CH ₂ -C(O)OC ₁ -C ₆ alkyl,- C(O)N(R ¹⁰ ) ₂ , -C(O)N(H)-CN, -C(O)N(H)OH, -C(O)N(H)-SO ₂ -C _1- C ₆ alkyl, -N(H)-SO ₂ -C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylsulfonyl, tetrazolyl or -S(O) ₂ -N(R ¹⁰ ) ₂ ; And each J ^{2 is} independently 4-6 membered heterocycloalkyl, -O-(4-6 membered heterocycloalkyl), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl alkane Oxy, phenyl C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halo, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkyl Oxy, OH, C ₁ -C ₆ hydroxyalkyl, CN, C ₁ -C ₆ cyanoalkyl, C ₂ -C ₆ alkynyl, C ₃ -C ₆ cycloalkylethynylene, C ₃ -C ₆ Cycloalkyl, 4-6 membered heterocycloalkyl, NO ₂ or -N(R ¹⁰ ) ₂ , with the restriction that when J ^{2 is} connected to nitrogen, J ^{2 is} not -O-(4-6 membered heterocycloalkane Group), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl alkoxy, phenyl C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkoxy, halo, C ₁ -C ₆ haloalkoxy, OH, CN, C ₂ -C ₆ alkynyl, C ₃ -C ₆ cycloalkylethynylene or -N(R ¹⁰ ) ₂ .

The phrase "where R ^{1 is} optionally substituted by 1 G ¹ group and 1-3 G ² groups" is intended to include where R ^{1 is} optionally substituted by 1 G ¹ group, and R ^{1 is} optionally substituted by 1-3 Examples of substitution with one G ² group and R ¹ optionally substituted with one G ¹ group and 1-3 G ^{2 groups.} This explanation applies to all variables described in the present invention (such as R ¹ , and J ¹ and J ² relative to R ⁵ ), which may be subject to more than one other variable (such as G ¹ and G ² or J ¹ and J ^{2) as appropriate.} )replace. Sub-Example of Example 1

Example 1 ( a1 ) of the present invention is related to Example 1, where: L is a bond, -CH ₂ -CH ₂ -, -(CH ₂ ) _1-2 -CH=CH-(CH ₂ ) _0-1 -, -CR ² R ³ -, -C(O)- or -S(O) ₂ -; The restriction is that when A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , and A ⁴ is When R ⁵ , X ¹ is N, X ² is C, and X ³ is C, L is a bond.

或

，其中4-6員環烷基、5-6員環烯基、苯基或5-9員雜芳基各自視情況經一個-L² -J¹ 基團及0-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子； 或當連接至氮時，R⁵ 為4-6員環烷基、5-6員環烯基、苯基或5-9員雜芳基，其中4-6員環烷基、5-6員環烯基、苯基或5-9員雜芳基各自視情況經1個-L² -J¹ 基團及1-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子。 Example 1 ( a2 ) of the present invention relates to Example 1, wherein when connected to a carbon, R ⁵ is 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl, 5-9 membered heteroaryl Group, 5-6 membered heterocycloalkyl

or

, Wherein the 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl or 5-9 membered heteroaryl group each has one -L ² -J ¹ group and 0-4 J ² groups as appropriate Substitution, the restriction is that J ^{1 is} directly bonded to a carbon atom; or when connected to nitrogen, R ⁵ is 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl or 5-9 membered heteroaryl , Wherein 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl or 5-9 membered heteroaryl group are each optionally connected with 1 -L ² -J ¹ group and 1-4 J ² groups Group substitution, the restriction condition is that J ^{1 is} directly bonded to a carbon atom.

Example 1 ( a ) of the present invention relates to Example 1, in which: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, and X ² is C and X ³ is N; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, X ² is C and X ³ is C; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, X ² is C, and X ³ is C.

Example 1 ( b ) of the present invention is related to Example 1, in which: A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, and X ² is C and X ³ is C; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, X ² is C, and X ³ is C.

Example 1 ( c ) of the present invention is related to Example 1, in which: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, and X ² is C and X ³ are N.

Example 1 ( d ) of the present invention is related to Example 1, in which: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, and X ² is C and X ³ is C.

Example 1 ( e ) of the present invention is related to Example 1, in which: A ¹ is R ⁶ , A ² does not exist, A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, X ² is N And X ³ is C.

Embodiment 1 ( f ) of the present invention is related to Embodiment 1, in which: A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, and X ² is C and X ³ is C.

Example 1 ( g ) of the present invention is related to Example 1, in which: A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, and X ² is C and X ³ is C.

Example 1 ( h ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f) or 1(g), where L is a key.

Example 1 ( i ) of the present invention relates to Example 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e) , 1(f) or 1(g), where L is a bond or -CR ² R ³ -.

Example 1 ( j ) of the present invention relates to Example 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e) , 1(f) or 1(g), where L is -CR ² R ³ -.

Example 1 ( j ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f) or 1(g), where L is -(CH ₂ ) _1-2 -CH=CH-(CH ₂ ) _0-1 -.

Example 1 ( k ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f) or 1(g), where L is -C(O)-.

Embodiment 1 ( l ) of the present invention relates to Embodiment 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f) or 1(g), where L is -S(O) ₂ -.

Example 1 ( m ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k) or 1(l), where R ¹ is a phenyl group or a 5-9 membered heteroaryl group, Wherein R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups.

Example 1 ( o ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k) or 1(l), where R ¹ is the case through 1 G ¹ group and 1 -3 phenyl groups substituted by ^{G 2 groups.}

Example 1 ( P ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k) or 1(l), where R ¹ is the case through 1 G ¹ group and 1 -5-9 membered heteroaryl substituted by 3 G ^{2 groups.}

Example 1 ( q ) of the present invention relates to Example 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e) , 1(f), 1(g), 1(h), 1(i), 1(j), 1(k) or 1(l), where R ¹ is C ₃ -C ₆ cycloalkyl or C _5- C ₆ cycloalkenyl, where R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups.

Example 1 ( r ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k) or 1(l), where R ¹ is 4-9 membered heterocycloalkyl or 5- 6-membered heterocycloalkenyl, where R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups.

或

，其中4-6員環烷基、5-6員環烯基、苯基或5-9員雜芳基各自視情況經一個L² -J¹ 基團及0-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子。 Example 1 ( s ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q) or 1(r), wherein R ^{5 is} connected to carbon and is 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl, 5-9 membered heteroaryl, 5-6 membered heterocycloalkyl,

or

, Wherein 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl or 5-9 membered heteroaryl are each optionally substituted with one L ² -J ¹ group and 0-4 J ² groups , The restriction is that J ^{1 is} directly bonded to the carbon atom.

Example 1 ( t ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q) or 1(r), wherein R ^{5 is} connected to nitrogen and is 4-6 membered cycloalkyl, 5-6 cycloalkenyl, phenyl, or 5-9 membered heteroaryl, wherein 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl or 5-9 membered heteroaryl are each substituted with 1 -L ² -J ¹ group and 1-4 J ² groups as appropriate , The restriction is that J ^{1 is} directly bonded to the carbon atom.

Example 1 ( u ) of the present invention is related to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q), 1(r), 1(s) or 1(t), where J ¹ is -C(O)OH or -C(O)OC ₁ -C ₆ alkyl.

Embodiment 1 ( v ) of the present invention relates to Embodiment 1, 1 (a1), 1 (a2), 1 (a), 1 (b), 1 (c), 1 (d), 1 (e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q), 1(r), 1(s) or 1(t), where J ¹ is -C(O)OH.

Example 1 ( w ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q), 1(r), 1(s) or 1(t), where J ¹ is -C(O)OC ₁ -C ₆ alkyl or CH ₂ -C(O)OC ₁ -C ₆ alkyl.

Example 1 ( x ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q), 1(r), 1(s) or 1(t), where J ¹ is -C(O)N(R ¹⁰ ) ₂ , -C(O)N(H) -CN or -C(O)N(H)OH.

Example 1 ( y ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q), 1(r), 1(s) or 1(t), where J ¹ is -C(O)N(H)-SO ₂ -C ₁ -C ₆ alkyl, -N(H)-SO ₂ -C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylsulfonyl or -S(O) ₂ -N(R ¹⁰ ) ₂ .

Example 1 ( z ) of the present invention relates to Examples 1, 1(a1), 1(a2), 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q), 1(r), 1(s) or 1(t), where J ¹ is tetrazolyl.

The ^{tetrazolyl in the definition of J 1} is the carboxylic acid isostere and other carboxylic acid isosteres that can be used in its position, such as Meanwell, "The Outline of Some Current Tactical Applications of Bioelectronic Isosteres in Drug Design (Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design)", "Journal of Medicinal Chemistry", dx.doi.org/10.1021/jm1013693, the carboxylic acid isostere described in Figure 25 , Which is incorporated by reference in its entirety.

In another embodiment of embodiment ¹ , J 1 can be a carboxylic acid isostere as described in Meanwell.

或

，其中4-6員環烷基、環己烯基、苯基、5-6員雜芳基或5-6員雜環烷基各自視情況經一個J¹ 基團及0-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子； 或當連接至氮時，R⁵ 為4-6員環烷基、環己烯基、苯基或5-6員雜芳基，其中4-6員環烷基、環己烯基、苯基或5-6員雜芳基各自視情況經1個-L² -J¹ 基團及1-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子； R⁶ 為含有至少一個氮原子之五員雜芳基，其中雜芳基視情況經1-2個R⁸ 基團取代； R⁷ 為H、鹵基或C₁ -C₅ 烷基； R⁸ 為C₁ -C₄ 烷基或C₁ -C₂ 烷氧基C₁ -C₂ 伸烷基； 各R¹⁰ 獨立地為H、C₁ -C₅ 烷基、C₁ -C₅ 鹵烷基或環丙基； 各R¹¹ 獨立地為H、C₁ -C₅ 烷基或C₁ -C₅ 鹵烷基，或兩個R¹¹ 基團與所述兩個R¹¹ 所連接之碳原子共同連接以形成環丙基； 各R¹² 為H； G¹ 為CN、C₁ -C₆ 氰基烷基、C₁ -C₅ 氰基烷基伸乙炔基、C₂ -C₅ 烯基C₁ -C₅ 伸烷基、C₁ -C₅ 烷基磺醯基、C₁ -C₅ 烷基磺醯基C₁ -C₅ 伸烷基、-N(R¹⁰ )₂ 、二-C₁ -C₅ 烷基胺基-C₁ -C₅ 伸烷基、C₁ -C₅ 烷基胺基-C₁ -C₅ 伸烷基、胺基C₁ -C₅ 伸烷基、-C(O)-C₁ -C₅ 烷基、-C(O)-C₁ -C₅ 羥基烷基、-C(O)-C₁ -C₅ 鹵烷基、-C(O)OR¹² 、-C₁ -C₃ 伸烷基-C(O)OR¹² 、-C(O)-N(H)-C₃ -C₆ 環烷基、C₃ -C₆ 環烷基、C₃ -C₆ 環烷基C₁ -C₅ 伸烷基、C₃ -C₆ 環烷基C₂ -C₅ 伸炔基、4-6員雜環烷基、-C(O)-N(R¹⁰ )₂ 、-C₁ -C₅ 伸烷基-C(O)-N(R¹⁰ )₂ 或苯基C₁ -C₅ 烷氧基，限制條件為當G¹ 連接至氮原子時，G¹ 不為CN； 各G² 獨立地為CN、鹵基、C₁ -C₅ 烷基、C₁ -C₅ 鹵烷基、C₁ -C₅ 烷氧基、C₁ -C₅ 鹵烷氧基、OH、側氧基、C₁ -C₅ 羥基烷基，限制條件為當G² 連接至氮原子時，G² 不為CN、鹵基、C₁ -C₅ 烷氧基、C₁ -C₅ 鹵烷氧基或OH； J¹ 為-C(R¹¹ )₂ -C(O)OH、-C(O)OH、-C(O)O-C₁ -C₅ 烷基、CH₂ -C(O)O-C₁ -C₅ 烷基、-C(O)N(R¹⁰ )₂ 、-C(O)N(H)-CN、-C(O)N(H)OH、-C(O)N(H)-SO₂ -C₁ -C₅ 烷基、-N(H)-SO₂ -C₁ -C₅ 烷基、C₁ -C₅ 烷基磺醯基、四唑基或-S(O)₂ -N(R¹⁰ )₂ ；及 各J² 獨立地為4-6員雜環烷基、-O-(4-6員雜環烷基)、-O-C₃ -C₆ 環烷基、C₃ -C₆ 環烷基烷氧基、苯基C₁ -C₅ 烷氧基、C₁ -C₅ 烷基、C₁ -C₅ 烷氧基、鹵基、C₁ -C₅ 鹵烷基、C₁ -C₅ 鹵烷氧基、OH、C₁ -C₅ 羥基烷基、CN、C₁ -C₅ 氰基烷基、C₂ -C₅ 炔基、C₃ -C₆ 環烷基伸乙炔基、C₃ -C₆ 環烷基、4-6員雜環烷基或-N(R¹⁰ )₂ ，限制條件為當J² 連接至氮時，J² 不為-O-(4-6員雜環烷基)、-O-C₃ -C₆ 環烷基、C₃ -C₆ 環烷基烷氧基、苯基C₁ -C₅ 烷氧基、C₁ -C₅ 烷氧基、鹵基、C₁ -C₅ 鹵烷氧基、OH、CN、C₂ -C₆ 炔基、C₃ -C₆ 環烷基伸乙炔基或-N(R¹⁰ )₂ 。實施例 2 之子實施例 Example 2 of the present invention relates to the compound of Example 1 or Example 1 (a1), wherein: R ¹ is phenyl, 5-6 membered heteroaryl, C ₃ -C ₆ cycloalkyl, C _5- C ₆ cycloalkenyl, 4-6 membered heterocycloalkyl or 5-6 membered heterocycloalkenyl, wherein R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups; R ³ is H, C ₁ -C ₆ alkyl, C ₁ -C ₆ cyanoalkyl, C ₁ -C ₆ haloalkyl, C ₃ -C ₆ cycloalkyl or 5-6 membered heteroaryl; R ⁴ is H , OH, C ₁ -C ₂ alkyl or C ₁ -C ₂ haloalkyl; when connected to carbon, R ⁵ is 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered hetero Aryl, 5-6 membered heterocycloalkyl,

or

, Wherein 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered heteroaryl or 5-6 membered heterocycloalkyl are each optionally connected to a J ¹ group and 0-4 J ² Group substitution, the restriction is that J ^{1 is} directly bonded to a carbon atom; or when connected to nitrogen, R ⁵ is 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5-6 membered heteroaryl, Wherein 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5-6 membered heteroaryl are each substituted by 1 -L ² -J ¹ group and 1-4 J ² groups as appropriate, with restrictions The condition is that J ^{1 is} directly bonded to a carbon atom; R ⁶ is a five-membered heteroaryl group containing at least one nitrogen atom, wherein the heteroaryl group is optionally ^{substituted by 1-2 R 8} groups; R ⁷ is H, halo Or C ₁ -C ₅ alkyl; R ⁸ is C ₁ -C ₄ alkyl or C ₁ -C ₂ alkoxy C ₁ -C ₂ alkylene; each R ^{10 is} independently H, C ₁ -C ₅ Alkyl, C ₁ -C ₅ haloalkyl or cyclopropyl; each R ^{11 is} independently H, C ₁ -C ₅ alkyl or C ₁ -C ₅ haloalkyl, or two R ¹¹ groups are The two ^{carbon atoms connected by R 11} are connected together to form a cyclopropyl group; each R ¹² is H; G ¹ is CN, C ₁ -C ₆ cyanoalkyl, C ₁ -C ₅ cyanoalkylethynylene , C ₂ -C ₅ alkenyl C ₁ -C ₅ alkylene, C ₁ -C ₅ alkylsulfonyl, C ₁ -C ₅ alkylsulfonyl C ₁ -C ₅ alkylene, -N( R ¹⁰ ) ₂ , di-C ₁ -C ₅ alkylamino group -C ₁ -C ₅ alkylene group, C ₁ -C ₅ alkylamino group -C ₁ -C ₅ alkylene group, amino group C _1- C ₅ alkylene, -C(O)-C ₁ -C ₅ alkyl, -C(O)-C ₁ -C ₅ hydroxyalkyl, -C(O)-C ₁ -C ₅ haloalkyl, -C(O)OR ¹² , -C ₁ -C ₃ alkylene-C(O)OR ¹² , -C(O)-N(H)-C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₅ alkylene, C ₃ -C ₆ cycloalkyl, C ₂ -C ₅ alkynylene, 4-6 membered heterocycloalkyl, -C( O)-N(R ¹⁰ ) ₂ , -C ₁ -C ₅ alkylene-C(O)-N(R ¹⁰ ) ₂ or phenyl C ₁ -C ₅ alkoxy, the restriction is that when G ^{1 is} connected To the nitrogen atom, G ^{1 is} not CN; each G ^{2 is} independently CN, halo, C ₁ -C ₅ alkyl, C ₁ -C ₅ haloalkyl, C ₁ -C ₅ alkoxy, C ₁ -C ₅ haloalkoxy, OH, pendant oxy, C ₁ -C ₅ hydroxyalkyl, with the restriction that when G ^{2 is} connected to a nitrogen atom, G ^{2 is} not CN, halo, C ₁ -C ₅ alkane Oxy, C ₁ -C ₅ haloalkoxy or OH; J ¹ is -C (R ¹¹ ) ₂ -C(O)OH, -C(O)OH, -C(O)OC ₁ -C ₅ alkyl, CH ₂ -C(O)OC ₁ -C ₅ alkyl, -C( O)N(R ¹⁰ ) ₂ , -C(O)N(H)-CN, -C(O)N(H)OH, -C(O)N(H)-SO ₂ -C ₁ -C ₅ Alkyl, -N(H)-SO ₂ -C ₁ -C ₅ alkyl, C ₁ -C ₅ alkylsulfonyl, tetrazolyl or -S(O) ₂ -N(R ¹⁰ ) ₂ ; and Each J ^{2 is} independently 4-6 membered heterocycloalkyl, -O-(4-6 membered heterocycloalkyl), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl alkoxy , Phenyl C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkyl, C ₁ -C ₅ alkoxy, halo, C ₁ -C ₅ haloalkyl, C ₁ -C ₅ haloalkoxy , OH, C ₁ -C ₅ hydroxyalkyl, CN, C ₁ -C ₅ cyanoalkyl, C ₂ -C ₅ alkynyl, C ₃ -C ₆ cycloalkylethynylene, C ₃ -C ₆ cycloalkane Group, 4-6 membered heterocycloalkyl or -N(R ¹⁰ ) ₂ , the restriction is that when J ^{2 is} connected to nitrogen, J ^{2 is} not -O-(4-6 membered heterocycloalkyl), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl alkoxy, phenyl C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkoxy, halo, C ₁ -C ₅ haloalkane Oxy, OH, CN, C ₂ -C ₆ alkynyl, C ₃ -C ₆ cycloalkylethynylene or -N(R ¹⁰ ) ₂ . Sub-Example of Example 2

Example 2 ( a ) of the present invention is related to Example 2, in which: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, and X ² is C and X ³ is N; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, X ² is C and X ³ is C; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, X ² is C, and X ³ is C.

Example 2 ( b ) of the present invention is related to Example 2, in which: A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, and X ² is C and X ³ is C; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, X ² is C, and X ³ is C.

Example 2 ( c ) of the present invention is related to Example 2, in which: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, and X ² is C and X ³ are N.

Example 2 ( d ) of the present invention is related to Example 2, in which: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, and X ² is C and X ³ is C.

Example 2 ( e ) of the present invention is related to Example 2, in which: A ¹ is R ⁶ , A ² does not exist, A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is C, X ² is N And X ³ is C.

Embodiment 2 ( f ) of the present invention is related to Embodiment 2, in which: A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, and X ² is C and X ³ is C.

Example 2 ( g ) of the present invention is related to Example 2, in which: A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, and X ² is C and X ³ is C.

Example 2 ( h ) of the present invention relates to Example 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f) or 2(g), Where L is a key.

Example 2 ( i ) of the present invention relates to Example 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f) or 2(g), Where L is a key or -CR ² R ³ -.

Example 2 ( j ) of the present invention relates to Example 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f) or 2(g), Where L is -CR ² R ³ -.

Example 2 ( j ) of the present invention relates to Example 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f) or 2(g), Where L is -(CH ₂ ) _1-2 -CH=CH-(CH ₂ ) _0-1 -.

Example 2 ( k ) of the present invention relates to Example 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f) or 2(g), Where L is -C(O)-.

Embodiment 2 ( l ) of the present invention relates to embodiment 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f) or 2(g), Where L is -S(O) ₂ -.

Example 2 ( m ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k) or 2(l), where R ¹ is a phenyl group or a 5- to 6-membered heteroaryl group, where R ¹ is subject to 1 G ¹ Group and 1-3 G ² groups.

Example 2 ( o ) of the present invention relates to Example 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k) or 2(l), where R ¹ is benzene substituted with 1 G ¹ group and 1-3 G ² groups as appropriate base.

Example 2 ( p ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k) or 2(l), where R ¹ is optionally substituted by 1 G ¹ group and 1-3 G ² groups -6 membered heteroaryl.

Example 2 ( q ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k) or 2(l), wherein R ¹ is C ₃ -C ₆ cycloalkyl or C ₅ -C ₆ cycloalkenyl, wherein R ¹ Optionally substituted by 1 G ¹ group and 1-3 G ² groups.

Example 2 ( r ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k) or 2(l), wherein R ¹ is 4-9 membered heterocycloalkyl or 5-6 membered heterocycloalkenyl, wherein R ¹ Optionally substituted by 1 G ¹ group and 1-3 G ² groups.

或

，其中4-6員環烷基、環己烯基、苯基、5-6員雜芳基或5-6員雜環烷基各自視情況經一個-L² -J¹ 基團及0-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子。 Example 2 ( s ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q) or 2(r), wherein R ^{5 is} connected to carbon and is 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl,

or

, Wherein 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered heteroaryl or 5-6 membered heterocycloalkyl are each optionally connected to ^{a -L 2 -J 1} group and 0- Four J ² groups are substituted, and the restriction is that J ^{1 is} directly bonded to a carbon atom.

Example 2 ( t ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q) or 2(r), wherein R ^{5 is} connected to nitrogen and is 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5-6 membered heteroaryl, wherein 4-6 membered cycloalkyl, cyclohexenyl , Phenyl or 5-6 membered heteroaryl groups are each substituted with 1 -L ² -J ¹ group and 1-4 J ² groups as appropriate, and the restriction condition is that J ^{1 is} directly bonded to a carbon atom.

Example 2 ( u ) of the present invention relates to Example 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q), 2(r), 2(s) or 2(t), where J ¹ is -C(O)OH or -C(O)OC ₁ -C ₅ alkyl.

Example 2 ( v ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q), 2(r), 2(s) or 2(t), where J ¹ is -C(O)OH.

Example 2 ( w ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q), 2(r), 2(s) or 2(t), where J ¹ is -C(O)OC ₁ -C ₅ alkyl or -CH ₂ -C(O)OC ₁ -C ₅ alkyl.

Example 2 ( x ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q), 2(r), 2(s) or 2(t), where J ¹ is -C(O)N(R ¹⁰ ) ₂ , -C(O)N(H)-CN or -C(O)N( H) OH.

Example 2 ( y ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q), 2(r), 2(s) or 2(t), where J ¹ is -C(O)N(H)-SO ₂ -C ₁ -C ₅ alkyl, -N(H)-SO ₂ -C ₁ -C ₅ alkyl, C ₁ -C ₅ alkylsulfonyl or -S(O) ₂ -N(R ¹⁰ ) ₂ .

Example 2 ( z ) of the present invention relates to Examples 2, 2(a), 2(b), 2(c), 2(d), 2(e), 2(f), 2(g), 2(h), 2(i), 2(j), 2(k), 2(l), 2(m), 2(n), 2(o), 2(p), 2(q), 2(r), 2(s) or 2(t), where J ¹ is tetrazolyl.

， 或其醫藥學上可接受之鹽、溶劑合物、互變異構體、立體異構體或氘化類似物。實施例 3 之子實施例 Example 3 of the present invention relates to the compound of Example 1 or 2, which has formula II(a), II(b) or II(c)

, Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog thereof. Sub-Example of Example 3

Example 3 ( a1 ) of the present invention relates to Example 3 having formula II(a) or II(b).

Example 3 ( a ) of the present invention relates to Example 3 having formula II(a).

Example 3 ( b ) of the present invention relates to Example 3 having formula II(b).

Example 3 ( c ) of the present invention relates to Example 3 having formula II(c).

Embodiment 3 ( d ) of the present invention relates to embodiment 3, 3(a1), 3(a), 3(b) or 3(c), where L is a key.

Embodiment 3 ( e ) of the present invention relates to embodiment 3, 3(a1), 3(a), 3(b) or 3(c), where L is a bond or -CR ² R ³ -.

Embodiment 3 ( f ) of the present invention relates to embodiment 3, 3(a1), 3(a), 3(b) or 3(c), where L is -CR ² R ³ -.

Example 3 ( g ) of the present invention relates to Example 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e) or 3(f), Wherein R ¹ is a phenyl group or a 5-6 membered heteroaryl group, where R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups.

Example 3 ( h ) of the present invention relates to Example 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e) or 3(f), Wherein R ¹ is a phenyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 3 ( i ) of the present invention relates to Example 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e) or 3(f), Wherein R ¹ is a 5-6 membered heteroaryl group substituted by 1 G ¹ group and 1-3 G ^{2 groups as appropriate.}

Example 3 ( j ) of the present invention relates to Example 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e) or 3(f), Wherein R ¹ is C ₃ -C ₆ cycloalkyl or C ₅ -C ₆ cycloalkenyl, wherein R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups.

Example 3 ( k ) of the present invention relates to Example 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e) or 3(f), Wherein R ¹ is 4-9 membered heterocycloalkyl or 5-6 membered heterocycloalkenyl, wherein R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups.

或

，其中4-6員環烷基、環己烯基、苯基、5-6員雜芳基或5-6員雜環烷基各自視情況經一個-L² -J¹ 基團及0-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子。 Example 3 (l) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j) or 3(k), where R ^{5 is} connected to carbon and is 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5 -6 membered heteroaryl, 5-6 membered heterocycloalkyl,

or

, Wherein 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered heteroaryl or 5-6 membered heterocycloalkyl are each optionally connected to ^{a -L 2 -J 1} group and 0- Four J ² groups are substituted, and the restriction is that J ^{1 is} directly bonded to a carbon atom.

Example 3 ( m ) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j) or 3(k), where R ^{5 is} connected to nitrogen and is 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5 -6 membered heteroaryl group, in which 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5-6 membered heteroaryl groups each have 1 -L ² -J ¹ group and 1-4 as appropriate The J ² group is substituted, and the restriction condition is that J ^{1 is} directly bonded to a carbon atom.

Example 3 ( n ) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j), 3(k), 3(l) or 3(m), where J ¹ is -C(O)OH or -C(O ) OC ₁ -C ₅ alkyl.

Example 3 ( o ) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j), 3(k), 3(l) or 3(m), where J ¹ is -C(O)OH.

Example 3 ( p ) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j), 3(k), 3(l) or 3(m), where J ¹ is -C(O)OC ₁ -C ₅ alkane Group or -CH ₂ -C(O)OC ₁ -C ₅ alkyl.

Example 3 ( q ) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j), 3(k), 3(l) or 3(m), where J ¹ is -C(O)N(R ¹⁰ ) ₂ , -C(O)N(H)-CN or -C(O)N(H)OH.

Example 3 ( r ) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j), 3(k), 3(l) or 3(m), where J ¹ is -C(O)N(H)-SO ₂ -C ₁ -C ₅ alkyl, -N(H)-SO ₂ -C ₁ -C ₅ alkyl, C ₁ -C ₅ alkylsulfonyl or -S(O) ₂ -N(R ¹⁰ ) ₂ .

Example 3 ( s ) of the present invention relates to Examples 3, 3(a1), 3(a), 3(b), 3(c), 3(d), 3(e), 3(f), 3(g), 3(h), 3(i), 3(j), 3(k), 3(l) or 3(m), where J ¹ is tetrazolyl.

， 或其醫藥學上可接受之鹽、溶劑合物、互變異構體、立體異構體或氘化類似物。實施例 4 之子實施例 Example 4 of the present invention relates to a compound such as any one of Examples 1-3 (including any sub-embodiments thereof), which has any one of formula III(a)-III(f):

, Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog thereof. Sub-Example of Example 4

The embodiment 4 ( a1 ) of the present invention is related to the embodiment 4, which has any one of formula III(a), III(c), III(d), III(e) or III(f). Example 4 ( a2 ) of the present invention relates to Example 4, which has any one of formula III(a), III(c) or III(d).

The embodiment 4 ( a ) of the present invention is related to the embodiment 4, which has any one of formula III(a), III(b), III(c) or III(d).

Embodiment 4 ( b ) of the present invention relates to Embodiment 4, which has either formula III(e) or III(f).

Example 4 ( c ) of the present invention relates to Example 4, which has formula III(a).

Example 4 ( d ) of the present invention relates to Example 4, which has formula III(b).

Example 4 ( e ) of the present invention relates to Example 4, which has formula III(c).

Example 4 ( f ) of the present invention relates to Example 4, which has formula III(d).

Example 4 ( g ) of the present invention relates to Example 4, which has formula III(e).

Example 4 ( h ) of the present invention relates to Example 4, which has formula III(f).

Example 4 ( i ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g) or 4(h), where R ¹ is a phenyl group or a 5-6 membered heteroaryl group, where R ^{1 is} optionally connected to 1 G ¹ group and 1-3 G ² groups团 Replacement.

Example 4 ( j ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g) or 4(h), where R ¹ is a phenyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 4 ( k ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g) or 4(h), where R ¹ is a 5-6 membered heteroaryl group substituted with 1 G ¹ group and 1-3 G ^{2 groups as appropriate.}

Example 4 ( l ) of the present invention is related to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g) or 4(h), where R ¹ is C ₃ -C ₆ cycloalkyl or C ₅ -C ₆ cycloalkenyl, where R ¹ optionally passes through 1 G ¹ group and 1-3 G ² groups are substituted.

Example 4 ( m ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g) or 4(h), where R ¹ is 4-9 membered heterocycloalkyl or 5-6 membered heterocycloalkenyl, where R ¹ optionally passes through 1 G ¹ group and 1-3 G ² groups are substituted.

或

，其中4-6員環烷基、環己烯基、苯基、5-6員雜芳基或5-6員雜環烷基各自視情況經一個-L² -J¹ 基團及0-4個J² 基團取代，限制條件為J¹ 直接鍵結至碳原子。 Example 4 ( n ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l) or 4(m), where R ^{5 is} connected to carbon and is 4- 6-membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl,

or

, Wherein 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered heteroaryl or 5-6 membered heterocycloalkyl are each optionally connected to ^{a -L 2 -J 1} group and 0- Four J ² groups are substituted, and the restriction is that J ^{1 is} directly bonded to a carbon atom.

Example 4 ( o ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l) or 4(m), where R ^{5 is} connected to nitrogen and is 4- 6-membered cycloalkyl, cyclohexenyl, phenyl, or 5-6 membered heteroaryl, wherein 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5-6 membered heteroaryl groups are each as appropriate One -L ² -J ¹ group and 1-4 J ² groups are substituted, and the restriction condition is that J ^{1 is} directly bonded to a carbon atom.

Example 4 ( p ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l), 4(m), 4(n) or 4(o), Wherein J ¹ is -C(O)OH or -C(O)OC ₁ -C ₅ alkyl.

Example 4 ( q ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l), 4(m), 4(n) or 4(o), Wherein J ¹ is -C(O)OH.

Example 4 ( r ) of the present invention relates to Examples 4, 4(a1), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l), 4(m), 4(n) or 4(o), where J ¹ is- C(O)OC ₁ -C ₅ alkyl or -CH ₂ -C(O)OC ₁ -C ₅ alkyl.

Example 4 ( s ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l), 4(m), 4(n) or 4(o), Wherein J ¹ is -C(O)N(R ¹⁰ ) ₂ , -C(O)N(H)-CN or -C(O)N(H)OH.

Example 4 ( t ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l), 4(m), 4(n) or 4(o), Where J ¹ is -C(O)N(H)-SO ₂ -C ₁ -C ₅ alkyl, -N(H)-SO ₂ -C ₁ -C ₅ alkyl, C ₁ -C ₅ alkyl sulfonate醯基 or -S(O) ₂ -N(R ¹⁰ ) ₂ .

Example 4 ( u ) of the present invention relates to Examples 4, 4(a1), 4(a2), 4(a), 4(b), 4(c), 4(d), 4(e), 4(f), 4(g), 4(h), 4(i), 4(j), 4(k), 4(l), 4(m), 4(n) or 4(o), Wherein J ¹ is tetrazolyl.

Example 5 of the present invention relates to a compound as in any one of Examples 1-4 (including any sub-embodiments thereof), wherein R ⁶ is:

。實施例 6 之子實施例： Example 6 of the present invention relates to a compound as in any one of Examples 1-5 (including any sub-embodiments thereof), wherein R ⁶ is:

. Sub- Example of Example 6:

Example 6 ( a ) of the present invention relates to Example 6, wherein R ⁶ is:

Example 6 ( b ) of the present invention relates to Example 6, wherein R ⁶ is:

Example 6 ( c ) of the present invention relates to Example 6, wherein R ⁶ is:

Example 7 of the present invention relates to a compound as in any one of Examples 1-6 (including any sub-embodiments thereof), wherein R ⁴ is H, OH, CF ₃ or CH ₃ . Sub-Example of Example 7

Example 7 ( a ) of the present invention relates to Example 7, wherein R ⁴ is H, CF ₃ or CH ₃ .

Example 7 ( b ) of the present invention relates to Example 7, wherein R ⁴ is H.

Example 7 ( c ) of the present invention relates to Example 7, wherein R ⁴ is CF ₃ or CH ₃ .

Example 7 ( d ) of the present invention relates to Example 7, wherein R ⁴ is CH ₃ .

Example 8 of the present invention relates to a compound such as any one of Examples 1, 2, 3, 5, 6 or 7 (where appropriate, including any sub-embodiments thereof), wherein L is a bond, CH _2- , -(CH ₂ ) ₂ -, CH(CH ₃ )-, CH(CH ₂ CH ₃ )-, -C(O)-, -CH(C ₃ -C ₆ cycloalkyl)-, -CH(pyridine Group)-, -C(CH ₃ )(pyridyl)-, -S(O) ₂ -or -C(H)(CH ₂ CN)-. The term "where appropriate" as used in the embodiments and sub-embodiments of the present invention means to exclude inappropriate instances in which the scope of the previous sub-embodiment is narrower than the latter. For example, the scope of Example 8 is broader than that of Example 2(h)-2(l), so Example 8 cannot be applied to sub-embodiment 2(h)-2(l). This explanation of the embodiments and sub-embodiments in the present invention applies to all examples, regardless of whether the term "where appropriate" is used. Sub-Example of Example 8

Embodiment 8 ( a ) of the present invention relates to Embodiment 8, where L is a key.

Embodiment 8 ( b ) of the present invention relates to Embodiment 8, wherein L is -CH ₂ -, -(CH ₂ ) ₂ -, CH(CH ₃ )- or CH(CH ₂ CH ₃ )-.

Example 8 ( c ) of the present invention relates to Example 8, where L is -C(O)- or -S(O) ₂ -.

Example 8 ( d ) of the present invention relates to Example 8, wherein L is -CH(C ₃ -C ₆ cycloalkyl)-.

Example 8 ( e ) of the present invention relates to Example 8, wherein L is -CH(pyridyl)- or -C(CH ₃ )(pyridyl)-.

Example 8 ( f ) of the present invention relates to Example 8, where L is -C(H)(CH ₂ CN)-.

Example 9 of the present invention relates to a compound as in any one of Examples 1-8 (including any sub-embodiments thereof when appropriate), wherein R ¹ is phenyl, pyridyl, pyrimidinyl, pyridazinyl, Pyrazolyl, C ₃ -C ₆ cycloalkyl, cyclohexenyl, morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl, tetrahydro-2H-furyl, oxetanyl, nitrogen Etidine, tetrahydro-2H-piperanyl, 1,1-tetrahydro-2H-thiopiperanyl, 1-oxotetrahydro-2H-thiopiperanyl, tetrahydro-2H-thiopiperan Pyranyl, tetrahydrothienyl or thienyl. Wherein R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups. Sub-Example of Example 9

Example 9 ( a ) of the present invention relates to Example 9, wherein R ¹ is phenyl, pyridyl or pyrimidinyl, wherein R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups .

Example 9 ( b ) of the present invention is related to Example 9, wherein R ¹ is a C ₃ -C ₆ cycloalkyl or cyclohexynyl group, wherein R ¹ optionally has 1 G ¹ group and 1-3 The G ² group is substituted.

Example 9 ( c ) of the present invention relates to Example 9, wherein R ¹ is morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl, tetrahydro-2H-furanyl, tetrahydro-2H-piperan Group, 1,1-dioxide tetrahydro-2H-thiopiperanyl, 1-oxide tetrahydro-2H-thiopiperanyl, tetrahydro-2H-thiopiperanyl or tetrahydrothiophenyl, wherein R ¹ Optionally substituted by 1 G ¹ group and 1-3 G ² groups.

Example 9 ( d ) of the present invention relates to Example 9, wherein R ¹ is a phenyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( f ) of the present invention relates to Example 9, wherein R ¹ is a pyridyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( g ) of the present invention relates to Example 9, wherein R ¹ is a pyrimidinyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( h ) of the present invention relates to Example 9, wherein R ¹ _{is a C 3} -C ₆ cycloalkyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( j ) of the present invention relates to Example 9, wherein R ¹ is a morpholino group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( k ) of the present invention relates to Example 9, wherein R ¹ is a piperazinyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( 1 ) of the present invention relates to Example 9, wherein R ¹ is a piperidinyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( m ) of the present invention relates to Example 9, wherein R ¹ is a pyrrolidinyl group substituted with 1 G ¹ group and 1-3 G ² groups as appropriate.

Example 9 ( n ) of the present invention relates to Example 9, wherein R ¹ is a tetrahydro-2H-furyl group substituted with 1 G ¹ group and 1-3 G ^{2 groups as appropriate.}

Example 9 ( o ) of the present invention relates to Example 9, wherein R ¹ is tetrahydro-2H-piperanyl substituted with 1 G ¹ group and 1-3 G ^{2 groups as appropriate.}

Example 9 ( p ) of the present invention relates to Example 9, wherein R ¹ is tetrahydro-2H-thiopiperanyl substituted with 1 G ¹ group and 1-3 G ^{2 groups as appropriate.}

Example 10 of the present invention relates to a compound as in any one of Examples 1-9 (including any sub-embodiments thereof when appropriate), wherein: R ¹ is (a), (b), (c), (D), (e), (f), (g), (h), (i), (j), (k), (l) or (m): (a) As the case may be _{C 3} -C ₆ cycloalkyl substituted with 1-3 G ² groups, where G ² is F, cyano or -CH ₂ CN; (b) As appropriate, 1 G ¹ group and 1-3 Phenyl substituted by G ² group, where G ¹ is benzyloxy, -C(=CH ₂ )CH ₃ , -C(O)OH, -C(O)NH ₂ , -C(O)N( H)-Cyclopropyl, cyclopropyl, cyano or -SO ₂ CH ₃ ; and each G ^{2 is} independently -OCHF ₂ , Cl, F, -OCH ₃ , -OCF ₃ , CH ₃ , CF _{3 and-} C(CH ₃ ) ₂ -OH; (c) Optionally ^{, pyridyl substituted with 1 G 1} group and 1-2 G ² groups, where G ¹ is -C(O)OH, -C(O ) NH ₂ , cyclopropyl or cyclopropyl alkynylene; and each G ^{2 is} independently F, CN, OCH ₃ , CF ₃ , CH ₃ , OH, -CH(CH ₃ ) ₂ and Cl; (d) depending on In the case ^{of pyrazolyl substituted with 1 G 1} group and 1-2 G ² groups, the restriction is that when R ¹ is pyrazolyl, L is a bond, where -NH- or =CH- can be substituted ^{The G 1} of the hydrogen atom is -CH ₂ -SO ₂ -CH ₃ , -(CH ₂ ) ₂ -N(CH ₃ ) ₂ , cyclopropyl, -CH ₂ -cyclopropyl, -(CH ₂ ) _2- CN or -CH ₂ C(O)N(CH ₃ ) ₂ ^{; and each G 2 that} can replace the hydrogen atom of -NH- or =CH- is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ halo Alkyl and hydroxy C ₁ -C ₆ alkyl; (e) _{pyrimidinyl substituted with -NH 2} , -N(CH ₃ ) ₂ , OCH ₃ , n-azetidinyl or cyclopropyl as appropriate; f) Pyridazinyl group; (g) 1-2 C ₁ -C ₆ alkyl group, C ₁ -C ₆ haloalkyl group, hydroxy C ₁ -C ₆ alkyl group, Cl and F are each independently Group-substituted tetrahydro-2H-piperanyl; (h) as the case may be 1-2 independently C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, hydroxy C ₁ -C ₆ Tetrahydro-2H-furanyl substituted by alkyl, Cl and F groups; (i) 1-2 independently C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl and Is the hydroxyl C ₁ -C ₆ alkyl group substituted? Alkyl; (j) oxetanyl; (k) 1-2 independently C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, and hydroxy C ₁ -C ₆ Alkyl group substituted piperidinyl group; (1) 1-2 independently C ₁ -C ₆ alkyl group, C ₁ -C ₆ haloalkyl group, hydroxy C ₁ -C ₆ alkyl group Cyclohexenyl substituted by the groups of, Cl and F; or (m) thienyl. Sub-Example of Example 10

， 其中： G³ 為H、OCH₃ 、N-氮雜環丁烷基、NH₂ 、-N(CH₃ )₂ 、環丙基； G⁴ 為H、CH₃ 、-CH₂ CH₃ 、-(CH₂ )N(CH₃ )₂ 、-CH₂ -SO₂ -CH₃ 、-CH(CH₃ )₂ 、-CH₂ C(CH₃ )₂ (OH)、環丙基、-CH₂ -環丙基、-(CH₂ )₂ -CN或-CH₂ C(O)N(CH₃ )₂ ； G⁵ 為H或OH； G⁶ 為H或CH₃ ；及 G⁷ 為H、CH₃ 、-(CH₂ )N(CH₃ )₂ 、-SO₂ -CH₃ 、-CH₂ -SO₂ -CH₃ 、-CH(CH₃ )₂ 、 -CH₂ C(CH₃ )₂ (OH)、環丙基、-CH₂ -環丙基、-(CH₂ )₂ -CN、-CH₂ C(O)N(CH₃ )₂ 、-C(O)OC(CH₃ )₃ 、-C(O)CH₃ 或-C(O)C(CH₃ )₃ 。實施例 11 之子實施例 Example 11 of the present invention relates to a compound as in any one of Examples 1-7 (including any sub-embodiments thereof when appropriate), wherein -LR ¹ is:

, Where: G ³ is H, OCH ₃ , N-azetidinyl, NH ₂ , -N(CH ₃ ) ₂ , cyclopropyl; G ⁴ is H, CH ₃ , -CH ₂ CH ₃ ,- (CH ₂ )N(CH ₃ ) ₂ , -CH ₂ -SO ₂ -CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ C(CH ₃ ) ₂ (OH), cyclopropyl, -CH _2- Cyclopropyl, -(CH ₂ ) ₂ -CN or -CH ₂ C(O)N(CH ₃ ) ₂ ; G ⁵ is H or OH; G ⁶ is H or CH ₃ ; and G ⁷ is H, CH ₃ , -(CH ₂ )N(CH ₃ ) ₂ , -SO ₂ -CH ₃ , -CH ₂ -SO ₂ -CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ C(CH ₃ ) ₂ (OH) , Cyclopropyl, -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -CH ₂ C(O)N(CH ₃ ) ₂ , -C(O)OC(CH ₃ ) ₃ , -C (O)CH ₃ or -C(O)C(CH ₃ ) ₃ . Sub-Example of Example 11

。 Example 11 ( a ) of the present invention is related to Example 11, where -LR ¹ is:

.

。 Example 11 ( b ) of the present invention is related to Example 11, where -LR ¹ is:

.

Example 11 ( c ) of the present invention is related to Example 11, where -LR ¹ is:

。 Example 11 ( d ) of the present invention relates to Example 11, where -LR ¹ is:

.

Embodiment 12 of the present invention relates to a compound as in embodiment 11 (including any sub-embodiments thereof when appropriate), wherein: G ¹ is benzyloxy, -C(=CH ₂ )CH ₃ , -C( O)OH, -C(O)NH ₂ , -C(O)N(H)-cyclopropyl, cyclopropyl, -CH ₂ -cyclopropyl, cyclopropylalkynylene, -CH ₂ -SO ₂ -CH ₃ , -SO ₂ -CH ₃ , -(CH ₂ )N(CH ₃ ) ₂ , -(CH ₂ ) ₂ -N(CH ₃ ) ₂ , -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -C(O)OC(CH ₃ ) ₃ , -C(O)CH ₃ and -C(O)C(CH ₃ ) ₃ , -CH ₂ C(O)N(CH ₃ ) ₂ , Cyano group or -SO ₂ CH ₃ ; and each G ^{2 is} independently -OCHF ₂ , -OCH ₂ F, Cl, F, -OCH ₃ , OH, -OCF ₃ , CH ₃ , -CH(CH ₃ ) ₂ , CF ₃ , -CH ₂ CN, CH ₂ C(CH ₃ ) ₂ (OH), and -C(CH ₃ ) ₂ -OH.

Example 13 of the present invention relates to the compound of Example 11, wherein -LR ¹ is:

Embodiment 14 of the present invention relates to the compound of embodiment 13, wherein G ¹ is benzyloxy, -C(=CH ₂ )CH ₃ , -C(O)OH, -C(O)NH ₂ ,- C(O)N(H)-cyclopropyl, cyclopropyl, -CH ₂ -cyclopropyl, cyclopropyl alkynylene, -CH ₂ -SO ₂ -CH ₃ , -SO ₂ -CH ₃ , -( CH ₂ )N(CH ₃ ) ₂ , -(CH ₂ ) ₂ -N(CH ₃ ) ₂ , -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -C(O)OC(CH ₃ ) ₃ , -C(O)CH ₃ , -C(O)C(CH ₃ ) ₃ , -CH ₂ C(O)N(CH ₃ ) ₂ , cyano or -SO ₂ CH ₃ ; and each G ² Independently -OCHF ₂ , -OCH ₂ F, Cl, F, -OCH ₃ , OH, -OCF ₃ , CH ₃ , -CH(CH ₃ ) ₂ , CF ₃ , -CH ₂ CN, CH ₂ C(CH ₃ ) ₂ (OH) and -C(CH ₃ ) ₂ -OH.

。實施例 15 之子實施例 Example 15 of the present invention relates to a compound as in any one of Examples 1-14 (including any sub-embodiments thereof when appropriate), wherein when connected to a carbon, R ⁵ is:

. Sub-Example of Example 15

Example 15 ( a ) of the present invention relates to Example 15, wherein R ⁵ is:

Example 15 ( b ) of the present invention relates to Example 15, wherein R ⁵ is:

Example 15 ( c ) of the present invention relates to Example 15, wherein R ⁵ is:

。 Example 15 ( d ) of the present invention relates to Example 15, wherein R ⁵ is:

.

Example 15 ( d ) of the present invention relates to Example 15, wherein R ⁵ is:

。 Example 15 ( e ) of the present invention relates to Example 15, wherein R ⁵ is:

.

實施例 16 之子實施例 Example 16 of the present invention relates to a compound as in any one of Examples 1-14 (including any sub-embodiments thereof when appropriate), wherein R ⁵ is:

Sub-Example of Example 16

。 Example 16 ( a ) of the present invention relates to Example 16, wherein R ⁵ is:

.

。 Example 16 ( b ) of the present invention relates to Example 16, wherein R ⁵ is:

.

。 Example 16 ( c ) of the present invention relates to Example 16, wherein R ⁵ is:

.

。 Example 16 ( d ) of the present invention relates to Example 16, wherein R ⁵ is:

.

。 Example 16 ( e ) of the present invention relates to Example 16, wherein R ⁵ is:

.

。 Example 16 ( f ) of the present invention relates to Example 16, wherein R ⁵ is:

.

。 Example 16 ( g ) of the present invention relates to Example 16, wherein R ⁵ is:

.

。 Example 16 ( h ) of the present invention relates to Example 16, wherein R ⁵ is:

.

Example 17 of the present invention relates to a compound as in any one of Examples 1-14 (including any sub-embodiments thereof when appropriate), wherein R ⁵ is:

。實施例 18 之子實施例 Example 18 of the present invention relates to a compound as in any one of Examples 1-14 (including any sub-embodiments thereof when appropriate), wherein R ⁵ is:

. Sub-Example of Example 18

。 Example 18 ( a ) of the present invention relates to Example 18, wherein R ⁵ is:

.

Example 18 ( b ) of the present invention relates to Example 18, where R ⁵ is:

。 Example 18 ( c ) of the present invention relates to Example 18, wherein R ⁵ is:

.

Example 18 ( d ) of the present invention relates to Example 18, wherein R ⁵ is:

。 Example 18 ( e ) of the present invention relates to Example 18, wherein R ⁵ is:

.

Example 19 of the present invention relates to a compound as in any one of Examples 15-18 (including any sub-embodiments thereof when appropriate), wherein R ⁵ is: J ¹ is -C(O)OH, -C (O)OCH ₃ , -CH ₂ C(O)OH, -C(O)N(H)CH ₃ , -C(O)NH ₂ , tetrazolyl, -SO ₂ CH ₃ , -C(O) N(H)CN, C(O)N(H)OH, -SO ₂ NH ₂ , -SO ₂ NH-cyclopropyl, -C(O)N(H)SO ₂ CH ₃ ; and each J ^{2 is} independent Ground is -O-cyclobutyl, -OCH ₂ -phenyl, -O-cyclopropyl, -O-CH ₂ -cyclopropyl, cyclopropylethynylene, CN, OH, cyclopropyl, F, Cl , -OCH ₃ , -OCHF ₂ , OCF ₃ , -OCH ₂ CF ₃ , -OCH ₂ CHF ₂ , -OCH(CH ₃ ) ₂ , -CH ₂ CH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ and CH ₃ .

Embodiment 20 of the present invention relates to the compound of embodiment 19 , wherein: J ¹ is -C(O)OH or -C(O)OCH ₃ ; and each J ^{2 is} independently F, Cl, -OCH ₃ , -OCHF ₂ , OCF ₃ , -OCH ₂ CF ₃ , -OCH ₂ CHF ₂ , -OCH(CH ₃ ) ₂ , -CH ₂ CH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ and CH ₃ .

或其醫藥學上可接受之鹽、溶劑合物、互變異構體、立體異構體或氘化類似物，其中： R⁵ 為：

； J¹ 為-C(O)OH或-C(O)OCH₃ ； 各J² 獨立地為F、Cl、-OCH₃ 、-OCHF₂ 、OCF₃ 、-OCH₂ CF₃ 、-OCH₂ CHF₂ 、-OCH(CH₃ )₂ 、-CH₂ CH₃ 、-OCH₂ CH₃ 、-OCH₂ CH₂ CH₃ 及CH₃ ； -L-R¹ 為

， 其中G¹ 為苯甲氧基、-C(=CH₂ )CH₃ 、-C(O)OH、-C(O)NH₂ 、-C(O)N(H)-環丙基、環丙基、-CH₂ -環丙基、環丙基伸炔基、-CH₂ -SO₂ -CH₃ 、-SO₂ -CH₃ 、-(CH₂ )N(CH₃ )₂ 、-(CH₂ )₂ -N(CH₃ )₂ 、-CH₂ -環丙基、-(CH₂ )₂ -CN、-C(O)OC(CH₃ )₃ 、-C(O)CH₃ 、-C(O)C(CH₃ )₃ 、-CH₂ C(O)N(CH₃ )₂ 、CN或-SO₂ CH₃ ；及 各G² 獨立地為-OCHF₂ 、-OCH₂ F、Cl、F、-OCH₃ 、OH、-OCF₃ 、CH₃ 、-CH(CH₃ )₂ 、CF₃ 、CN、-CH₂ CN、CH₂ C(CH₃ )₂ (OH)及-C(CH₃ )₂ -OH。實施例 21 之子實施例 Example 21 of the present invention relates to the compound of Example 1, which has any one of formula IV(a)-IV(c):

Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog thereof, wherein: R ⁵ is:

; J ¹ is -C(O)OH or -C(O)OCH ₃ ; each J ^{2 is} independently F, Cl, -OCH ₃ , -OCHF ₂ , OCF ₃ , -OCH ₂ CF ₃ , -OCH ₂ CHF ₂ , -OCH(CH ₃ ) ₂ , -CH ₂ CH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ and CH ₃ ; -LR ¹ is

, Where G ¹ is benzyloxy, -C(=CH ₂ )CH ₃ , -C(O)OH, -C(O)NH ₂ , -C(O)N(H)-cyclopropyl, ring Propyl, -CH ₂ -cyclopropyl, cyclopropylalkynylene, -CH ₂ -SO ₂ -CH ₃ , -SO ₂ -CH ₃ , -(CH ₂ )N(CH ₃ ) ₂ , -(CH ₂ ) ₂ -N(CH ₃ ) ₂ , -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -C(O)OC(CH ₃ ) ₃ , -C(O)CH ₃ , -C( O)C(CH ₃ ) ₃ , -CH ₂ C(O)N(CH ₃ ) ₂ , CN or -SO ₂ CH ₃ ; and each G ^{2 is} independently -OCHF ₂ , -OCH ₂ F, Cl, F , -OCH ₃ , OH, -OCF ₃ , CH ₃ , -CH(CH ₃ ) ₂ , CF ₃ , CN, -CH ₂ CN, CH ₂ C(CH ₃ ) ₂ (OH) and -C(CH ₃ ) ₂ -OH. Sub-Example of Example 21

Example 21 ( a1 ) of the present invention relates to Example 21, which has formula IV(a) or formula IV(c).

Example 21 ( a ) of the present invention relates to Example 21, which has formula IV(a).

Example 21 ( b ) of the present invention relates to Example 21, which has formula IV(b).

Example 21 ( c ) of the present invention relates to Example 21, which has formula IV(c).

。 The embodiment 21 ( d ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 The embodiment 21 ( e ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 The embodiment 21 ( f ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 The embodiment 21 ( g ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 The embodiment 21 ( g ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 The embodiment 21 ( h ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 The embodiment 21 ( i ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

The embodiment 21 ( j ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

。 The embodiment 21 ( k ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 The embodiment 21 ( l ) of the present invention relates to any one of the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), wherein R ⁵ is:

.

。 Example 21 ( m ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 Example 21 ( n ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 Example 21 ( o ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 Example 21 ( p ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 Example 21 ( q ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 Example 21 ( r ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 Example 21 ( s ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 Example 21 ( t ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

。 The embodiment 21 ( u ) of the present invention relates to embodiments 21, 21 (a1), 21 (a), 21 (b) or 21 (c), 21 (d), 21 (e), 21 (f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

. The embodiment 21 ( v ) of the present invention is related to the embodiments 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

Example 21 ( w ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

。 Example 21 ( x ) of the present invention relates to Examples 21, 21(a1), 21(a), 21(b) or 21(c), 21(d), 21(e), 21(f), Any one of 21(g), 21(h), 21(i), 21(j), 21(k) or 21(l), where -LR ¹ is:

.

Example 22 relates to the compound of Example 1 of the present invention, which is selected from Table 1 of the present invention, or a pharmaceutically acceptable salt thereof.

The compounds covered herein are described with reference to the general formula and specific compounds. In addition, the compounds described herein can exist in a variety of different forms or derivatives, all of which fall within the scope of the present invention. Such forms or derivatives include, for example, tautomers, stereoisomers, racemic mixtures, regioisomers, salts, prodrugs (such as carboxylic acid esters), fusion forms, and active metabolites.

It should be understood that some compounds may exhibit tautomerism. In such cases, the chemical formula provided herein only clearly depicts one of the possible tautomeric forms. Therefore, it should be understood that the chemical formula provided herein is intended to represent any tautomeric form of the depicted compound and is not intended to be limited to the specific tautomeric form depicted by the schema of the chemical formula.

Similarly, some of the compounds of the present invention may exist in the form of stereoisomers as defined herein. All such single stereoisomers, racemates and mixtures thereof are intended to fall within the scope of the present invention. Unless stated to the contrary, all such stereoisomeric forms are included in the chemical formulas provided herein.

In some embodiments, the antipodal compound of the present invention contains at least 80% of a single isomer (60% enantiomeric excess ("ee") or diastereomeric excess ("de")), or At least 85% (70% ee or de), 90% (80% ee or de), 95% (90% ee or de), 97.5% (95% ee or de) or 99% (98% ee or de) The form. As generally understood by those familiar with the art, an optically pure compound with one antipodal center is a compound consisting essentially of one of two possible enantiomers (ie, enantiomeric Optically pure compounds with more than one antipodal center are diastereomerically pure and enantiomerically pure compounds. In some embodiments, the compound exists in an optically pure form.

For compounds in which the synthesis involves the addition of a single group at the double bond, especially the carbon-carbon double bond, the addition can be made at any of the atoms connected by the double bond. For such compounds, the present invention includes two such regioisomers.

In addition to the chemical formulas and compounds of the present invention described herein, the present invention also includes prodrugs (usually pharmaceutically acceptable prodrugs), active metabolic derivatives (active metabolites) and pharmaceutically acceptable salts thereof.

Unless stated to the contrary, the description of the compounds herein includes pharmaceutically acceptable salts of such compounds.

In some embodiments, the compound of the present invention is complexed with acid or base, including base addition salts, such as ammonium, diethylamine, ethanolamine, ethylenediamine, diethanolamine, tertiary butylamine, piperazine, meglumine; Acid addition salts, such as acetate, acetosalicylate, benzenesulfonate, camphorsulfonate, citrate, formate, fumarate, glutarate, hydrochloride , Maleate, methanesulfonate, nitrate, oxalate, phosphate, succinate, sulfate, tartrate, thiocyanate and tosylate; and amino acids, such as Alanine, arginine, aspartic acid, aspartic acid, cysteine, glutamic acid, glutamic acid, glycine, histidine, isoleucine, leucine, lysine Acid, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine. In some cases, the amorphous form of the complex is promoted by another treatment, such as by spray drying, mechanochemical methods (such as rolling), or microwave irradiation of the parent compound mixed with acid or base. Such methods may also include the addition of ionic and/or non-ionic polymer systems, including (but not limited to) hydroxypropyl methylcellulose acetate succinate (HPMCAS) and methacrylic acid copolymers (such as Eudragit® L100-55), which further stabilizes the amorphous nature of the composite. Such amorphous composites provide several advantages. For example, lowering the melting temperature relative to free alkali facilitates other processing (such as hot melt extrusion) to further improve the biomedical properties of the compound. In addition, amorphous composites are easily broken, thereby providing improved compression to load solids in capsule or lozenge form.

In addition, the chemical formula is intended to cover hydrated or fused and non-hydrated or non-soluble forms of the identified structure. For example, the indicated compounds include hydrated and non-hydrated forms. Other examples of solvates include the combination of the structure and a suitable solvent such as isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, or ethanolamine. III. Formulations and administration

Example 23 of the present invention relates to a pharmaceutical composition comprising a compound of an embodiment of the present invention (such as the compound of any one of Examples 1-22 (including any sub-embodiments thereof)) and medicine The acceptable carrier.

Example 24 of the present invention relates to the pharmaceutical composition of Example 23, which further comprises a second agent.

The suitable dosage form partly depends on the purpose or route of administration, such as oral, transdermal, transmucosal, inhalation or by injection (parenteral). Such a dosage form should allow the compound to reach the target cell. Other factors are well known in the art and include considerations such as toxicity and dosage forms that prevent the compound or composition from exerting its effect. Techniques and formulations are usually found in "The Science and Practice of Pharmacy", 21st edition, Lippincott, Williams and Wilkins, Philadelphia, PA, 2005 (incorporated by reference) .

The compounds of the present invention (ie, any of the compounds described in Examples 1-22 (including any sub-embodiments thereof)) can be formulated as pharmaceutically acceptable salts.

Carriers or excipients can be used to produce the composition. The carrier or excipient can be selected to facilitate the administration of the compound. Examples of carriers include calcium carbonate; calcium phosphate; various sugars such as lactose, glucose or sucrose; or starch types; cellulose derivatives; gelatin; vegetable oils; polyethylene glycols; and physiologically compatible solvents. Examples of physiologically compatible solvents include water for injection (WFI), physiological saline solution, and sterile solutions of dextrose.

The compounds can be administered by different routes, including intravenous, intraperitoneal, subcutaneous, intramuscular, oral, transmucosal, transrectal, transdermal, or inhalation. In some embodiments, the compound can be administered by oral administration. For oral administration, for example, the compound can be formulated into conventional oral dosage forms, such as capsules, lozenges, and liquid preparations, such as syrups, elixirs, and concentrated drops.

For inhalants, the compounds of the present invention can be formulated as dry powders or suitable solutions, suspensions or sprays. Powders and solutions can be formulated with suitable additives known in the art. For example, the powder may include a suitable powder base such as lactose or starch, and the solution may include propylene glycol, sterile water, ethanol, sodium chloride, and other additives such as acids, bases, and buffer salts. Such solutions or suspensions can be administered by inhalation, through nebulizers, pumps, atomizers or sprayers and the like. The compounds of the present invention can also be used in combination with other inhalation therapies, such as corticosteroids, such as fluticasone proprionate, beclomethasone dipropionate, triamcinolone acetonide, budesonide ) And mometasone furoate; beta agonists, such as albuterol, salmeterol, and formoterol; anticholinergic agents, such as ipratropium bromide Ipratroprium bromide or tiotropium; vasodilators, such as treprostinal and iloprost; enzymes, such as DNAase; therapeutic proteins; immunoglobulin antibodies; oligonucleosides Acids, such as single- or double-stranded DNA or RNA, siRNA; antibiotics, such as tobramycin; muscarinic receptor antagonists; leukotriene antagonists; interleukin antagonists; protease inhibitors; cromolyn Sodium; nedocril sodium; and sodium cromoside.

Pharmaceutical preparations for oral use can be obtained, for example, by combining the active compound with solid excipients, optionally grinding the resulting mixture, and optionally processing the mixture of granules after adding suitable auxiliaries to obtain lozenges or dragee cores. Suitable excipients are especially fillers, such as sugars, including lactose, sucrose, mannitol or sorbitol; cellulose preparations, such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methyl Cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose (CMC) and/or polyvinylpyrrolidone (PVP: povidone). If necessary, disintegrating agents may be added, such as cross-linked polyvinylpyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate.

Dragee cores have suitable coatings. For this purpose, concentrated sugar solutions can be used, which may optionally contain gum arabic, talc, polyvinylpyrrolidone, carbopol gel, polyethylene glycol (PEG) and/or titanium dioxide as appropriate. , Paint solution and suitable organic solvent or solvent mixture. Dyestuffs or pigments can be added to the tablet or dragee coating for identification or to characterize different combinations of active compound doses.

Pharmaceutical preparations that can be used orally include insertable capsules made of gelatin ("capsules"), and soft sealed capsules made of gelatin and a plasticizer (such as glycerin or sorbitol). The insertable capsules may contain active ingredients which are mixed with fillers such as lactose, binders such as starch, and/or lubricants such as talc or magnesium stearate, and optionally stabilizers. In soft capsules, the active compounds can be dissolved or suspended in suitable liquids such as fatty oils, liquid paraffin, or liquid polyethylene glycol (PEG). In addition, stabilizers can be added.

Alternatively, injection (parenteral administration) can be used, such as intramuscular, intravenous, intraperitoneal, and/or subcutaneous injection. For injection, the present invention is formulated in a sterile liquid solution (such as a physiologically compatible buffer or solution, such as physiological saline solution, Hank's solution or Ringer's solution) Compound. In addition, the compound can be formulated in a solid form and redissolved or suspended immediately before use. It can also be produced in freeze-dried form.

Administration can also be by transmucosal, topical, transdermal or inhalation means. For transmucosal, topical or transdermal administration, penetrants suitable for penetration barriers are used in the formulation. Such penetrants are generally known in the art, and for transmucosal administration, include, for example, bile salts and fusidic acid derivatives. In addition, detergents can be used to promote penetration. Transmucosal administration can be carried out, for example, via a nasal spray or suppository (transrectally or transvaginally).

The topical composition of the present invention can be formulated into oils, creams, lotions, ointments and the like by selecting suitable carriers known in the art. Suitable carriers include vegetable or mineral oils, white petrolatum (white soft paraffin), branched chain fats or oils, animal fats and high molecular weight alcohols (greater than C ₁₂ ). In another embodiment, the carrier is a substance in which the active ingredient is soluble. If necessary, it can also include emulsifiers, stabilizers, moisturizers and antioxidants, as well as agents that provide color or fragrance. Creams for topical application are formulated from a mixture of mineral oil, self-emulsifying beeswax and water, in which the active ingredients are dissolved in a small amount of solvent (such as oil). In addition, administration by transdermal means may include transdermal patches or dressings, such as bandages impregnated with active ingredients and optionally one or more carriers or diluents known in the art. For administration in the form of a transdermal delivery system, the dosage administration is of course continuous rather than intermittent throughout the dosage regimen.

Various amounts of the compound can be administered by standard procedures thereto, consider _50, biological half-life of the compound, the age of the individual, signs and weight, and factors such as the indication being treated, the compound IC was measured. The importance of these and other factors is well known to those skilled in the art. Generally, the dosage will be between about 0.01 and 50 mg/kg or 0.1 and 20 mg/kg of the individual being treated. Multiple doses can be used.

The compounds of the present invention can also be used in combination with other therapies used to treat the same diseases. Such combined use includes administering the compound and one or more other therapeutic agents at different times, or co-administering the compound and one or more other therapies. In some embodiments, the dosage may be for one or more of the compounds of the present invention or other therapeutic agents used in combination, and can be modified by methods well known to those skilled in the art, such as the dosage relative to the single Reduced compound or therapy used.

It should be understood that combined use includes use with other therapies, drugs, medical procedures, etc., where another therapy or procedure can be used at a different time (for example, in a short time, such as several hours (for example, 1, 2, 3, 4-24). Within hours), or within a longer period of time (eg 1-2 days, 2-4 days, 4-7 days, 1-4 weeks) compared with the compound of the present invention, or administered with the compound of the present invention Simultaneous administration. Combination use also includes use with one-time or infrequent administration of the therapy or medical procedure (such as surgery), and administration in a short or longer period of time before or after another therapy or procedure The compound of the present invention. In some embodiments, the present invention provides the compound of the present invention and the delivery of one or more other pharmaceutical therapeutic agents by different administration routes or by the same administration route. For the combined use of any administration route Including co-delivery of the compound of the present invention in any formulation and one or more other pharmaceutical therapeutics delivered by the same route of administration, including formulations in which two compounds are chemically linked in a way that maintains their therapeutic activity during administration In one aspect, another drug therapy can be co-administered with one or more of the compounds of the present invention. Co-administration is used to combine co-formulations or co-formulations including the administration of chemically-conjugated compounds, or between each other Two or more compounds in the independent formulations are administered within a short period of time (for example, within one hour, 2 hours, 3 hours, or at most 24 hours), which are administered by the same or different routes. Independent formulations Co-administration includes co-administration by delivery via one device (such as the same inhalation device, the same syringe, etc.), or by separate devices within a short time of each other. One of the compounds of the present invention and delivered by the same route Co-formulations for or multiple other drug therapies include co-preparation of materials so that they can be used by a device (including individual compounds combined in a formulation, or modified so that they are chemically bonded, but still retain their biological activity. Compound) administration. Such chemically joined compounds can have a connection that is substantially maintained in vivo, or the connection can be decomposed in vivo to separate the two active components. IV. Method of Use

The methods and compounds will generally be used in the treatment of human individuals. However, it can also be used to treat similar or identical indications in other animal individuals.

In certain embodiments, the patient is 60 years of age or older and relapsed after first-line cancer therapy. In certain embodiments, the patient is 18 years of age or older and is relapsed or refractory after second-line cancer therapy. In certain embodiments, the patient is 60 years of age or older and is primarily refractory to first-line cancer therapy. In certain embodiments, the patient is 70 years of age or older and has not been previously treated. In certain embodiments, the patient is 70 years of age or older and is not eligible for cancer therapy and/or is unlikely to benefit from cancer therapy.

In certain embodiments, the therapeutically effective amount used in the methods provided herein is at least 10 mg/day. In certain embodiments, the therapeutically effective amount is 10, 50, 90, 100, 135, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1200, 1300 , 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2200, 2500 mg/day. In other embodiments, the therapeutically effective amount is 10, 50, 90, 100, 135, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2200, 2500, 3000, 3500, 4000, 4500, 5000 mg/day or more. In certain embodiments, the compound is administered continuously.

In certain embodiments, provided herein is a method for treating a disease or condition mediated by EP300 or CBP by administering at least 10, 50, 90, 10 to a mammal suffering from the disease or condition. 100, 135, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2200, 2500, 3000, 3500, 4000, 4500, 5000 mg/day any one of the compounds described in the compound of one of Examples 1-22, or a pharmaceutically acceptable salt, deuteration thereof Analogs, tautomers or stereoisomers, and wherein the compound is administered on an empty stomach.

Example 25 of the present invention relates to a method for treating an individual suffering from a disease or condition mediated by EP300 or CBP, the method comprising administering to the individual an effective amount of one of Examples 1-22 Or a pharmaceutically acceptable salt, deuterated analog, tautomer or stereoisomer thereof, or a pharmaceutical composition such as one of Examples 23-24.

Embodiment 26 of the present invention relates to a method for treating an individual suffering from a disease or condition as in embodiment 25, wherein the disease or condition is a cancer with an inactivating mutation in CBP or EP300, or exists therein EP300 or CBP activated cancer.

Embodiment 27 of the present invention relates to a method for treating an individual suffering from a disease or condition as in embodiment 25, wherein the disease or condition is cancer that expresses an androgen receptor.

Embodiment 28 of the present invention relates to a method for treating an individual suffering from a disease or condition as in embodiment 25, wherein the disease or condition is a neoplastic disease, cancer, inflammatory disease, age-related disease, Cognitive disorders and neurodegenerative diseases.

Embodiment 29 of the present invention relates to a method for treating an individual suffering from a disease or condition as in embodiment 25, wherein the disease or condition is acral lentigines melanoma, acute eosinophilic leukemia, acute Red blood cell leukemia, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, bladder cancer, adenocarcinoma, adult T-cell leukemia/lymphoma, aggressive NK cells Leukemia, AIDS-related lymphoma, pleomorphic large cell lymphoma, hemangioimmunoblastic T-cell lymphoma, B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, B-cell lymphoma, bone cancer, Burki Burkitt's lymphoma, skin T-cell lymphoma, colorectal cancer, diffuse large B-cell lymphoma, enteropathy-associated T-cell lymphoma, follicular lymphoma, glioblastoma multiforme, Glioma, gastric cancer, liver and spleen T cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, lymphoma, acute lymphocytic leukemia, acute myelogenous leukemia, chronic lymphoma Globular leukemia, small cell lung cancer, non-small cell lung cancer, MALT lymphoma, malignant peripheral nerve sheath tumor, mantle cell lymphoma, marginal zone B cell lymphoma, mast cell leukemia, breast cancer, neuroblastoma, melanoma Tumor, merkel cell cancer, mesothelioma, multiple myeloma, neuroblastoma, neurofibroma, nodular melanoma, osteosarcoma, ovarian cancer, precursor T-lymphoblastic lymph Tumor, primary central nervous system lymphoma, primary exudative lymphoma, prostate cancer, pancreatic cancer, skin cancer, T-cell lymphoma, uveal melanoma, Alzheimer's disease, Parkinson's disease or colorectal cancer.

Embodiment 29 ( a ) of the present invention relates to the method for treating an individual suffering from a disease or condition as in embodiment 29, wherein the disease or condition is acute myeloid leukemia.

Embodiment 29 ( b ) of the present invention relates to the method for treating an individual suffering from a disease or condition as in embodiment 29, wherein the disease or condition is multiple myeloma.

Embodiment 29 ( c ) of the present invention relates to the method for treating an individual suffering from a disease or condition as in embodiment 29, wherein the disease or condition is prostate cancer.

Embodiment 29 ( d ) of the present invention relates to the method for treating an individual suffering from a disease or condition as in embodiment 29, wherein the disease or condition is prostate cancer.

Embodiment 30 of the present invention relates to a method for treating an individual suffering from a disease or condition as in embodiment 29, wherein the disease or condition is small cell lung cancer, non-small cell lung cancer, bladder cancer, non-Hodgge King’s lymphoma, acute myelogenous leukemia, multiple myeloma, diffuse large B-cell lymphoma, breast cancer, or prostate cancer.

Embodiment 31 of the present invention relates to a method for treating an individual suffering from a disease or condition as in embodiment 29, wherein the disease or condition is Alzheimer's disease or Parkinson's disease. V. Combination Therapy

EP300 and CBP modulators can be effectively combined with another pharmacologically active compound or two or more other pharmacologically active compounds, especially in the treatment of cancer. In one embodiment, the composition includes any one or more compounds as described herein and one or more compounds that are therapeutically effective for the same disease indication, wherein the compounds have a synergistic effect on the disease indication. In one embodiment, the composition includes any one or more compounds as described herein that are effective in treating cancer and one or more other compounds that are effective in treating the same cancer, and in addition, wherein the compounds are effective in treating cancer in a synergistic manner.

In another embodiment, the present invention provides a method for treating diseases or conditions mediated by EP300 or CBP by administering to an individual an effective amount of a composition comprising as described herein A combination of any one or more of the compounds and one or more other suitable therapies for the treatment of the disease.

Example 32 of the present invention relates to the method of any one of Examples 25-31 or any sub-embodiments thereof, which further comprises administering one or more other therapeutic agents.

Embodiment 33 of the present invention relates to the method of embodiment 32, wherein the one or more other therapeutic agents are one or more of the following: i) an alkylating agent, which is selected from adozelesin (adozelesin) , Altretamine, bizelesin, busulan, carboplatin, carboquone, carmustine, chlorambucil ( chlorambucil, cisplatin, cyclophosphamide, dacarbazine, estramustine, fotemustine, hepsulfam, ifosin Ifosfamide, improsulfan, irofulven, lomustine, mechlorethamine, melphalan, oxaliplatin , Piposulfan (piposulfan), semustine (semustine), streptozocin (streptozocin), temozolomide (temozolomide), thiotepa (thiotepa) and triosulfan (treosulfan); ii) antibiotics, which Selected from bleomycin, actinomycin D (dactinomycin), daunorubicin, cranberry (doxorubicin), epirubicin, idarubicin, Miele Menogaril, mitomycin, mitoxantrone, neocarzinostatin, pentostatin and plicamycin; iii) antimetabolites , Which is selected from the group consisting of: azacitidine, capecitabine, cladribine, clofarabine, cytarabine, diazide Decitabine, floxuridine, fludarabine, 5-fluorouracil, ftorafur, gemcitabine, hydroxyurea, mercaptopurine, methylamine Pterin (methotrexate), nelarbine (nelar abine), pemetrexed, raltitrexed, thioguanine and trimetrexate; iv) immunotherapeutics (including PD-1 or PD-L1 inhibitors) , Which is selected from alemtuzumab (alemtuzumab), bevacizumab (bevacizumab), cetuximab (cetuximab), galiximab (galiximab), gemtuzumab (gemtuzumab), Nivo Nivolumab, panitumumab, pembrolizumab, pertuzumab, rituximab, tositumomab, Trastuzumab and 90 Y ibritumomab tiuxetan; v) Hormone or hormone antagonist, which is selected from the group consisting of enzalutamide, abirate Abiraterone, anastrozole, androgen, buserelin, diethylstilbestrol, exemestane, flutamide, fulvestrant , Goserelin (goserelin), idoxifene (idoxifene), letrozole (letrozole), leuprolide (leuprolide), megestrol (magestrol), raloxifene (raloxifene), tamoxifen Tamoxifen and toremifene; vi) taxane selected from DJ-927, docetaxel, TPI 287, paclitaxel and DHA-paclitaxel; vii) Retinoids, which are selected from alitretinoin, bexarotene, fenretinide, isotretinoin and tretinoin; viii) alkaloids , Which is selected from etoposide, homoharringtonine, teniposide, vinblastine, vincristine, vindesine and vinorelbine Vinorelbine; ix) anti-angiogenesis agent selected from AE-941 (GW7 86034, Neovastat), ABT-510, 2-Methoxyestradiol, lenalidomide and thalidomide; x) Topoisomerase inhibitor, which is selected from Amsacrine, edotecarin, exatecan, irinotecan, SN-38 (7-ethyl-10-hydroxy-camptothecin), ruby Rubitecan, topotecan and 9-aminocamptothecin; xi) kinase inhibitor, which is selected from erlotinib and gefitinib , Flavopiridol, imatinib mesylate, lapatinib, sorafenib, sunitinib malate, AEE-788, AG-013736, AMG 706, AMN107, BMS-354825, BMS-599626, UCN-01 (7-hydroxystaurosporine), vemurafenib, dabrafenib, trametinib (Trametinib), cobimetinib, selumetinib, and vatalanib; xii) a targeted signal transduction inhibitor selected from the group consisting of bortezomib, Geer Geldanamycin and rapamycin; xiii) a biological response modifier selected from imiquimod, interferon-α and interleukin-2; xiv) IDO inhibitors; And xv) a chemotherapeutic agent, which is selected from the group consisting of 3-AP (3-amino-2-hydroxyaldehyde thiosemicarbazone), altrasentan, aminoglutethimide, anagrelide ), asparaginase, bryostatin-1, cilengitide, elesclomol, eribulin mesylate ( E7389), ixabepilone, lonidamine, masoprocol, mitoguanazone, oblimersen, sulindac, testosterone Lactone (tes tolactone), thiazofurin (tiazofurin), mTOR inhibitor, PI3K inhibitor, Cdk4 inhibitor, Akt inhibitor, Hsp90 inhibitor, farnesyl transferase inhibitor or aromatase inhibitor (anastrozoletrozole Simestane (anastrozole letrozole exemestane)); xvi) Mek inhibitor; xvii) Tyrosine kinase inhibitor; xviii) c-Kit mutant inhibitor, xix) EGFR inhibitor, PD-1 inhibitor or xx) table Genetic regulator.

Example 33 ( a ) of the present invention relates to the method as in Example 32, wherein the one or more other therapeutic agents are one or more of the following: i) an alkylating agent, which is selected from Adorexine , Hexamethylmelamine, Pezrexine, Busulfan, Carboplatin, Carboquinone, Carmustine, Chlorambucil, Cisplatin, Cyclophosphamide, Dacarbazine, Estramustine, Formaldehyde Stine, Hepfaam, Ifosfamide, Inprosufane, Irofofen, Lomustine, Mechlorethamine, Melphalan, Oxaliplatin, Piposhufan, Semustine , Streptozotocin, temozolomide, thiotepa and trioxifan; ii) antibiotics selected from the group consisting of bleomycin, actinomycin D, daunorubicin, cranberry, epirubicin, idabe Star, Minoril, Mitomycin, Mitoxantrone, New Tumor Suppressor Protein, Penstatin, and Pracamycin; iii) Antimetabolites, which are selected from the group consisting of: azacitidine , Capecitabine, cladribine, clofarabine, cytarabine, decitabine, fluridine, fludarabine, 5-fluorouracil, tegafur, gemcitabine, hydroxyurea, mercaptopurine, methyl Methotrexate, nelarabine, pemetrexed, raltitrexed, thioguanine and trimexate; iv) immunotherapeutic agent selected from PD-1 or PD-L1 inhibitors; v) hormone or hormone Antagonist, selected from the group consisting of enzalutamide, ranoxifen, abiraterone, anastrozole, androgen, buserelin, diethylstilbestrol, exemestane, flutamide, fulvastat Stran, goserelin, idoxifene, letrozole, leuprolide, megestrol, ranoxifen, tamoxifen and toremifene; vi) taxane, which is selected from DJ-927, docetaxel, TPI 287, paclitaxel and DHA-paclitaxel; vii) retinoids selected from the group consisting of aritritonin, becerotene, filitinib, isotretinoin and Retinoic acid; viii) alkaloids selected from the group consisting of etoposide, homoharringtonine, teniposide, vinblastine, vincristine, vindesine and vinorelbine; ix) anti-angiogenic agents, which are selected From AE-941 (GW786034, Sha'ailing), ABT-510, 2-methoxyestradiol, lenalidomide and thalidomide; x) a topoisomerase inhibitor, which is selected from amsacrine, Atcarin, Ixinotecan, Irinotecan, SN-38 (7-ethyl-10-hydroxy-camptothecin), Rubotecan, Topotecan and 9-aminocamptothecin; xi ) Kinase inhibitor, which is selected from the group consisting of erlotinib, gefitinib, flapinib, imatinib mesylate, lapatinib, sorafenib, sunitinib malate, AEE-788, AG-013736, AMG 706, AMN107, BMS-354825, BMS-599626, UCN-01 (7-hydroxy staurosporine), verofenib, dabrafenib, trametinib, cobitinib, Smetinib and fantalanib; xii) targeted signal transduction inhibitors, which are selected from bortezomib, geldanamycin, and rapamycin; xiii) biological response modifiers, which are selected from imiquine Mott, interferon-α and interleukin-2; xiv) IDO inhibitor; and xv) chemotherapeutic agent selected from the group consisting of 3-AP (3-amino-2-hydroxyaldethiocarbazone), atrasentan, amiluminide, anagrelide, aspartame Aminase, bryozotocin-1, cilengitide, elimol, eribulin mesylate (E7389), ixabepilone, clonidamine, masorofol, mitoguazone, olympin Limerson, sulindac, testosterone, thiazofurin, mTOR inhibitor, PI3K inhibitor, Cdk4 inhibitor, Akt inhibitor, Hsp90 inhibitor, farnesyl transferase inhibitor or aromatase inhibitor (A Nastrozole, letrozole, exemestane); xvi) Mek inhibitor; xvii) Tyrosine kinase inhibitor; xviii) c-Kit mutant inhibitor, xix) EGFR inhibitor, PD-1 inhibitor, or xx ) Epigenetic regulators.

Embodiment 34 of the present invention relates to the method of embodiment 33, wherein the one or more other therapeutic agents are epigenetic modulators, which are selected from the group consisting of: (a) DNA methyltransferase; ( b) Histone or protein methyltransferase; (c) Histone demethylase; (d) Histone deacetylase inhibitor; (f) Other chromatin remodeling agents; and (g) B BRD4 Inhibitor.

Embodiment 35 of the present invention relates to the method of embodiment 34, wherein the epigenetic modulator is a histone deacetylase inhibitor, which is selected from the group consisting of: vorinostat, Luo Romidepsin, chidamide, panobinostat, belinostat, valproic acid, mocetinostat, abes He (abexinostat), entinostat, resminostat, givinostat and quisinostat.

Embodiment 36 of the present invention relates to the method of embodiment 34, wherein the epigenetic modulator is a BRD4 inhibitor.

Example 37 of the present invention relates to the method of Example 33, wherein one or more other therapeutic agents are PD-1 inhibitors, quizartinib, enzalutamide, abiraterone ) Or BRD4 inhibitor.

Example 38 of the present invention relates to the method of Example 33, wherein one or more other therapeutic agents are enzalutamide and the disease is prostate cancer, including but not limited to castration-resistant prostate cancer.

Example 39 of the present invention relates to the method of Example 33, wherein one or more other therapeutic agents are abiraterone and the disease is prostate cancer, including but not limited to castration-resistant prostate cancer.

Bromodomains (eg, BET proteins such as BRD2, BRD3, BRD4 and/or BRDT) and diseases associated with abnormal expressions of bromodomains include, among others, cell proliferative disorders, cancer, chronic autoimmune and inflammatory conditions. Non-limiting examples of BET inhibitors include PLX1107, GSK1210151A, and GSK525762.

Histone deacetylase inhibitors (HDAC inhibitors) are cell growth inhibitors that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and/or apoptosis. HDAC inhibitors exert their anti-tumor effects by inducing changes in the expression of oncogenes or tumor suppressor factors, and by regulating the acetylation/deacetylation of histones and/or non-histone proteins (such as transcription factors). Histone acetylation and deacetylation play an important role in regulating chromatin topology and regulating gene transcription. Non-limiting examples of HDAC inhibitors include vorinostat, romidepsin, chidamide, pabinostatin, belinostatin, valproic acid, moxenostat, aberestat, enti Nott, Remino, Givernot, and Quicino. HDAC inhibitors have been widely used in psychiatry and neurology as mood stabilizers and antiepileptic agents. One example of this is valproic acid, which is sold as drugs under the trade names Depakene, Depakote, and Divalproex. HDAC inhibitors are also used as relievers of neurodegenerative diseases such as Alzheimer's disease and Huntington's disease.

In another embodiment, the present invention provides a method for treating cancer in an individual in need, by administering to the individual an effective amount of a composition comprising any one or A combination of multiple compounds and one or more other therapies or medical procedures that can effectively treat cancer. Other therapies or medical procedures include suitable anti-cancer therapies (e.g., drug therapy, vaccine therapy, gene therapy, photodynamic therapy) or medical procedures (e.g., surgery, radiation therapy, hyperthermia, bone marrow or stem cell transplantation). In one embodiment, one or more suitable anti-cancer therapies or medical procedures are selected from the following: treatment with chemotherapeutic agents (such as chemotherapeutic drugs), radiotherapy (such as x-rays, .γ-rays or electrons, Proton, neutron or α particle beam), high temperature heating (such as microwave, ultrasound, radiofrequency ablation), vaccine therapy (such as AFP gene hepatocellular carcinoma vaccine, AFP adenovirus vector vaccine, AG-858, allogeneic GM- CSF secretes breast cancer vaccine, dendritic cell peptide vaccine), gene therapy (such as Ad5CMV-p53 vector, adenovirus vector encoding MDA7, adenovirus 5-tumor necrosis factor alpha), photodynamic therapy (such as aminoacetoxypropionic acid) , Motexatin lutetium), surgery or bone marrow and stem cell transplantation. VI. Set

In another aspect, the present invention provides a kit comprising one or more compounds or pharmaceutically acceptable salts thereof as described in any one of the compounds in one of Examples 1-22 , Deuterated analogs, tautomers or stereoisomers, or pharmaceutical compositions such as one of Examples 23-24. In some embodiments, the compound or composition is packaged in, for example, vials, bottles, flasks, which can be further contained in, for example, boxes, envelopes, or bags. The compound or composition may be approved by the US Food and Drug Administration or similar regulatory agency for administration to mammals (eg, humans). The compounds or compositions may be approved for administration to mammals (such as humans) for EP300 or CBP-mediated diseases or conditions. The kits described herein may include written instructions and/or other instructions that the compound or composition is suitable or approved for administration to mammals (such as humans) for EP300 or CBP-mediated diseases or conditions . The compound or composition can be packaged in unit dose or single dose form, such as a single dose pill, capsule or the like. VII. Combination analysis method

The method of the present invention may involve an analytical method capable of detecting the binding of a compound to a target molecule. Such binding is at a statistically significant level and the confidence level is at least 90%, or at least 95, 97, 98, 99% or greater confidence level (analytical signal indicates the combination with the target molecule, that is, distinguished from the background). In some embodiments, a control is used to distinguish between target binding and non-specific binding. A variety of analysis methods for the combination of indicators of different target types are known and can be used in the present invention.

The binding compound may be characterized by its effect on the activity of the target molecule. Therefore, "low activity" compounds have an inhibitory concentration (IC ₅₀ ) or effective concentration (EC ₅₀ ) greater than 1 μM under standard conditions. "Very low activity" means that the IC ₅₀ or EC _{50 is} greater than 100 μM under standard conditions. "Very low activity" means that the IC ₅₀ or EC _{50 is} greater than 1 mM under standard conditions. "Intermediate activity" means an IC ₅₀ or EC ₅₀ of 200 nM to 1 μM under standard conditions. "Moderately high activity" means that the IC ₅₀ or EC ₅₀ is 1 nM to 200 nM. "High activity" means that the IC ₅₀ or EC _{50 is} less than 1 nM under standard conditions. The IC ₅₀ or EC _{50 is} defined as the concentration of the compound at which 50% of the measured activity of the target molecule (such as an enzyme or other protein) is lost or obtained relative to the observed activity range in the absence of the compound. The activity can be measured using methods known to those skilled in the art, for example, by measuring any detectable product or signal generated by the enzymatic reaction, or other activity of the protein being measured.

The "background signal" of the binding analysis method means the signal recorded under the standard conditions of the specific analysis method in the absence of a test compound, molecular skeleton or ligand that binds to the target molecule. Those skilled in the art will recognize that there are well-recognized methods that can be widely used to determine background signals.

。表面電漿共振 "Standard deviation" means the square root of the variance. Variance is a measure of the degree of distribution of the distribution. It is calculated as the average square deviation of each number from its average. For example, for numbers 1, 2, and 3, the average is 2 and the variance is:

. Surface Plasma Resonance

Surface plasmon resonance can be used to measure the bonding parameters, for example, using a BIAcore ^® chip coated with a fixed bonding component (Biacore, Japan). Use surface plasmon resonance to characterize the microscopic association and dissociation constants of the reaction between sFv or other ligands for the target molecule. Such methods are generally described in the following references which are incorporated herein by reference. Vely F. et al., (2000) "BIAcore ^® analysis for the interaction domain of the phosphorylated peptide -SH2 test structure ^{(BIAcore ® analysis to test phosphopeptide-} SH2 domain interactions)", " Molecular Biology (Methods in Molecular Biology )”, 121:313-21; Liparoto et al., (1999) “Biosensor analysis of the interleukin-2 receptor complex”, “Journal of Molecular Recognition ( Journal of Molecular Recognition, 12:316-21; Lipschultz et al., (2000) "Experimental design for analysis of complex kinetics using surface plasmon resonance" , "Methods", 20(3):310-8; Malmqvist., (1999) "BIACORE: an affinity biosensor system for characterization of biomolecular Interactions, "Biochemical Society Transactions", 27:335-40; Alfthan, (1998) "Surface plasmon resonance biosensors as a tool in antibody engineering a tool in antibody engineering)", "Biosensors &Bioelectronics",13:653-63; Fivash et al., (1998) "BIAcore for the interaction of giant molecules (BIAcore for macromolecular interaction), "Current Opinion in Biotechnology", 9:97-101; Price et al.; (199 8) "Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin", "Tumor "Tumour Biology" 19 Supplement 1:1-20; Malmqvist et al., (1997) "Biomolecular interaction analysis: affinity biosensor technology for functional analysis of proteins" biosensor technologies for functional analysis of proteins), "Current Opinion in Chemical Biology", 1:378-83; O'Shannessy et al., (1996) "Interpretation of deviations from pseudo-first-order kinetic behavior in the characterization of ligand binding by biosensor technology", "Analytical Biochemistry"", 236: 275-83; Malmborg et al., (1995) "BIAcore as a tool in antibody engineering", "Journal of Immunological Methods", 183: 7-13; Van Regenmortel, (1994) "Use of biosensors to characterize recombinant proteins", "Developments in Biological Standardization", 83:143-51; And O'Shannessy, (1994) "The Dynamic Rate of Macromolecular Interaction and the Equilibrium Binding Constant" Determination: Determination of kinetic rate and equilibrium binding constants for macromolecular interactions: a critique of the surface plasmon resonance literature, "Current Opinions in Biotechnology", 5:65 -71.

BIAcore ^® uses the optical properties of surface plasma resonance (SPR) to detect changes in the protein concentration of a polydextrose matrix (a polydextrose biosensor matrix) bound to the surface of the gold/glass sensor chip interface. In short, the protein is covalently bound to the polydextrose matrix at a known concentration and the ligand of the protein is injected through the polydextrose matrix. The near-infrared light directed to the opposite side of the sensor chip surface is reflected and also induces evanescent waves in the gold film, which in turn causes intensity pits of the reflected light at a specific angle (called the resonance angle). If the refractive index of the sensor chip surface changes (for example, by binding to a ligand that binds to a protein), the resonance angle will shift. This angular deviation can be measured and expressed as a resonance unit (RU), so that 1000 RU is equivalent to a change in surface protein concentration of ^{1 ng/mm 2.} These changes are shown with respect to time along the y-axis of the sensor map, which depicts the correlation and dissociation of any biological response. High throughput screening ( HTS ) analysis method

HTS usually uses automated analysis methods to search for a large number of compounds for the desired activity. Generally, HTS analysis is used to find new drugs by screening chemical substances that act on specific enzymes or molecules. For example, if the chemical substance does not activate the enzyme, it can be proved that it can effectively prevent the disease-causing process in the cell. The high-throughput method allows researchers to use machine operating systems and automatic result analysis to analyze thousands of different chemical substances for each target molecule extremely quickly.

As used herein, "high-throughput screening" or "HTS" refers to the rapid in vitro screening of a large number of compounds (libraries); usually tens of thousands to hundreds of thousands of compounds, using robotic screening analysis methods. Ultra-high-throughput screening (uHTS) usually refers to high-throughput screening accelerated to more than 100,000 tests per day.

To achieve high-throughput screening, it is advantageous to load samples on a multi-container carrier or platform. The multi-container carrier helps to measure the response of multiple candidate compounds at the same time. A porous microplate can be used as a carrier. Such porous microplates and the methods used in various analysis methods are known in the art and are commercially available.

The screening analysis method may include a control substance for the purpose of calibration and confirmation of the proper operation of the components of the analysis method. Usually includes a blank well, which contains all the reactants, but does not contain members of the chemical library. As another example, a known inhibitor (or activator) of an enzyme seeking a modulator can be incubated with a sample of the analysis method, and the resulting decrease (or increase) in enzyme activity can be used as a comparison or control. It will be appreciated that modulators can also be combined with enzyme activators or inhibitors to seek to inhibit enzyme activation or suppression that is otherwise caused by the presence of known enzyme modulators. Measure enzymatic and binding reactions during screening assays

Techniques for measuring the progress of enzymatic and binding reactions (for example in multi-container carriers) are known in the art and include (but are not limited to) the following.

Spectrophotometry and fluorescence spectrophotometry are well known in the art. Examples of such analysis methods include the use of colorimetric analysis methods for detecting peroxides, such as Gordon, AJ and Ford, RA, (1972) "Chemistry Work Guide: A Handbook of Practical Data, Techniques, and References (The Chemist's) Companion: A Handbook Of Practical Data, Techniques, And References), John Wiley and Sons, NY, page 437.

Fluorescence spectrometry can be used to monitor the production of reaction products. Fluorescence methods are generally more sensitive than absorption methods. The use of fluorescent probes is well known to those skilled in the art. For a review, see Bashford et al., (1987) "Spectrophotometry and Spectrofluorometry: A Practical Approach", pp. 91-114, IRL Press Ltd.; and Bell, ( 1981) "Spectroscopy In Biochemistry", Volume I, Pages 155-194, CRC Press.

In the fluorescence spectrophotometric method, the enzyme is exposed to a substrate that can change its endogenous fluorescence when processed by the target enzyme. Generally, the substrate is non-fluorescent and is converted to a fluorophore through one or more reactions. As non-limiting examples, using Amplex ^® Red reagent (Molecular Probes, Eugene, OR) to detect the activity of SMase. In order to use Amplex ^® Red to measure neurophospholipase activity, perform the following reaction. First, SMase hydrolyzes sphingomyelin to produce ceramide and phosphocholine. Second, alkaline phosphatase hydrolyzes phosphorylcholine to produce choline. Third, choline is oxidized to betaine by choline oxidase. Finally, in the presence of horseradish peroxidase, H ₂ O ₂ reacts with Amplex ^® Red to produce the fluorescent product Resorufin and use spectrofluorimetry to detect the signal from it.

Fluorescence polarization (FP) is based on the reduction of the molecular rotation speed of the fluorophore when bound to larger molecules (such as receptor proteins), taking into account the polarized fluorescence emission by the bound ligand. FP is determined empirically by measuring the vertical and horizontal components emitted by the fluorophore after excitation by plane polarized light. When the molecular rotation of the fluorophore decreases, the polarized emission increases. When the fluorophore binds to a larger molecule (that is, the receptor), it generates a greater polarization signal and slows down the rotation of the fluorophore's molecules. The magnitude of the polarization signal is quantitatively related to the degree of binding of the fluorescent ligand. Therefore, the polarization of the "binding" signal depends on the maintenance of high-affinity binding.

FP is a homogeneous technology and the reaction is extremely fast, which takes several seconds to several minutes to reach equilibrium. The reagents are stable and can be prepared in large quantities, resulting in high reproducibility. Because of these characteristics, FP has proven to be highly automatable, usually with a single, pre-mixed, tracer-receptor reagent, with a single incubation. For review, see Owicki et al., (1997), "Application of Fluorescence Polarization Assays in High-Throughput Screening", "Genetic Engineering News" , 17:27.

The reading of FP has nothing to do with emission intensity (Checovich, WJ et al., (1995) "Nature" 375:254-256; Dandliker, WB et al., (1981) "Methods in Enzymology" 74:3-28) and therefore insensitivity to the presence of colored compounds that can quench fluorescent emission, which is particularly desirable. FP and FRET (see below) are well suited to identify compounds that can block the interaction between sphingolipid receptors and their ligands. See, for example, Parker et al., (2000) "Development of high throughput screening assays using fluorescence polarization: Nuclear receptor-ligand binding and kinase/phosphatase analysis (Development of high throughput screening assays using fluorescence polarization: nuclear receptor-ligand-binding and kinase/phosphatase assays, "J Biomol Screen" 5:77-88.

The fluorophores derived from sphingolipids that can be used in the FP analysis method are commercially available. For example, Molecular Probes (Eugene, OR) currently sells sphingomyelin and a ceramide fluorophore. They are N-(4,4-difluoro-5,7-dimethyl-4-boron-3a,4a-diaza-s-dicyclopentacene-3-pentanyl)sphingamine Phosphocholine (BODIPY® FL C5-sphingomyelin); N-(4,4-difluoro-5,7-dimethyl-4-boron-3a,4a-diaza-s-dicyclopentadiene) Diocene-3-dodecanoyl) sphingosine phosphorylcholine (BODIPY® FL C12-sphingomyelin); and N-(4,4-difluoro-5,7-dimethyl-4-boron -3a,4a-Diaza-s-Dicyclopentacene-3-pentanyl) sphingosine (BODIPY ^® FL C5-ceramide). U.S. Patent No. 4,150,949 (Immunoanalysis for gentamicin) discloses luciferin-labeled gentamicin, including luciferin thiamine methyl gentamicin. Other fluorophores can be prepared using methods well known to those skilled in the art.

Exemplary normal and polarized fluorescence readers include the POLARION ^® fluorescence polarization system (Tecan AG, Hombrechtikon, Switzerland). Universal multiwell plate readers for other analytical methods can be used, such as VERSAMAX ^® reader and SPECTRAMAX ^® multiwell plate spectrophotometer (all from Molecular Devices)

Fluorescence resonance energy transfer (FRET) is another analytical method suitable for detecting mutual phases and has been described. See, for example, Heim et al., (1996) Curr. Biol. 6:178-182; Mitra et al., (1996) Gene 173:13-17; and Selvin et al., (1995) "Meth. Enzymol." 246:300-345. FRET detects the energy transfer between two fluorescent substances that have known excitation and emission wavelengths in close proximity. As an example, the protein can be expressed as a fusion protein with green fluorescent protein (GFP). When two fluorescent proteins are in close proximity, such as when the protein specifically interacts with a target molecule, resonance energy can be transferred from one excitation molecule to the other. Therefore, the emission spectrum shift of the sample can be measured by a fluorometer (such as an fMAX porous fluorometer (Molecular Devices, Sunnyvale Calif.)).

Scintillation proximity analysis (SPA) is an analysis method especially suitable for detecting interaction with target molecules. SPA is widely used in the pharmaceutical industry and has been described (Hanselman et al., (1997) "J. Lipid Res." 38: 2365-2373; Kahl et al., (1996) "Analytical Biochemistry ( Anal. Biochem.) 243:282-283; Undenfriend et al. (1987) Analytical Biochemistry 161:494-500). See also U.S. Patent Nos. 4,626,513 and 4,568,649 and European Patent No. 0,154,734. By using a commercially available system FLASHPLATE ^® coating of the scintillator plates (NEN Life Science Products, Boston, MA).

Target molecules can be bound to the scintillator plate by a variety of well-known methods. A scintillator plate can be used, which is derivatized to bind to a fusion protein, such as a GST, His6, or Flag fusion protein. When the target molecule is a protein complex or polymer, a protein or subunit can be first connected to the plate, and then another component of the complex is added under binding conditions to produce a bound complex.

In a typical SPA analysis method, the gene product in the expression cell will be radiolabeled and added to the well, and allowed to interact with the solid phase, which is the immobilized target molecule and scintillation coated in the well body. The analysis method can be immediately measured or balanced. Either way, when the radioactive label becomes close enough to the scintillator coating, it generates a signal that can be detected by a device such as the TOPCOUNT NXT ^® microplate scintillation counter (Packard BioScience Co., Meriden Conn.). If the radiolabeled performance product binds to the target molecule, the radiolabel remains close to the scintillator long enough to generate a detectable signal.

In contrast, labeled proteins that are not bound to the target molecule or bound only briefly will not stay close to the scintillator long enough to generate a signal above background. Any time spent near the scintillator caused by random Brownian motion will not generate a large amount of signal. Similarly, there may be residual unincorporated radiolabel used during the presentation step, but will not produce a significant signal because it will be in solution rather than interacting with the target molecule. Therefore, these non-binding interactions will cause a certain level of background signal that can be removed mathematically. If too much signal is obtained, salt or other modifiers can be directly added to the analysis plate until the required specificity is obtained (Nichols et al., (1998) "Analytical Biochemistry" 257:112-119). General Synthesis

The compounds can be prepared using the methods disclosed herein and their conventional modifications (which will be apparent from the disclosure herein) and methods well known in the art. In addition to the teachings in this article, conventional and well-known synthetic methods can also be used. The synthesis of the typical compounds described herein can be achieved as described in the following examples. If available, reagents can be purchased commercially, for example, from Sigma Aldrich or other chemical suppliers.

The compounds of the present invention can be prepared from readily available starting materials using, for example, the following general methods and procedures. It should be understood that when typical or preferred processing conditions (ie, reaction temperature, time, molar ratio of reactants, solvent, pressure, etc.) are given, other processing conditions may also be used unless otherwise stated. The optimal reaction conditions may vary with the specific reactants or solvents used, but such conditions can be determined by those skilled in the art through conventional optimization procedures.

In addition, it will be obvious to those skilled in the art that conventional protecting groups may be needed to prevent certain functional groups from undergoing undesired reactions. Suitable protecting groups for various functional groups and suitable conditions for protecting and deprotecting specific functional groups are well known in the art. For example, a large number of protecting groups are described in Wuts, PGM, Greene, TW and Greene, TW (2006), "Greene's protective groups in organic synthesis", Hoboken, NJ, Wiley-Interscience and Among the references cited.

In addition, the compounds of the present invention may contain one or more asymmetric or opposing centers. Therefore, if desired, such compounds can be prepared as pure stereoisomers (that is, individual enantiomers or diastereomers) or as concentrated mixtures of stereoisomers. Unless otherwise indicated, all such stereoisomers (and concentrated mixtures) are included within the scope of the present invention. Pure stereoisomers (or concentrated mixtures) can be prepared using, for example, optically active starting materials or stereoselective reagents well known in the art. Alternatively, the racemic mixture of such compounds can be separated using, for example, para-palm column chromatography, supercritical fluid chromatography, para-palm seed crystals, para-palm resolving agents, and similar methods.

The starting materials used in the following reactions are commonly known compounds or can be prepared by known procedures or their obvious modifications. For example, many starting materials are available from commercial suppliers, such as Aldrich Chemical Co. (Milwaukee, Wisconsin, USA), Bachem (Torrance, California, USA), Emka-Chemce or Sigma (St. Louis, Missouri, USA) ). Other starting materials can be prepared by the procedures described in standard reference texts or obvious modifications thereof, such as "Fieser and Fieser's Reagents for Organic Synthesis", No. 1- Volume 15 (John Wiley and Sons, 1991), Rodd's "Chemistry of Carbon Compounds", Volumes 1-5 and Supplements (Elsevier Science Publishers, 1989) "Organic Reactions", No. 1 Volume -40 (John Wiley, and Sons, 1991), March’s "Advanced Organic Chemistry" (John Wiley, and Sons, 5th Edition, 2001), and Larock’s "Comprehensive Organic Transformations" )" (VCH Publishers Inc., 1989).

It should also be understood that in any process, the addition of any substituent can cause the production of a variety of isomeric products (including but not limited to enantiomers or one or more diastereomers), any of which may be All can be separated and purified using conventional techniques. When enantiomerically pure or enriched compounds are required, anti-palp chromatography and/or enantiomerically pure or enriched starting materials can be used in this technique as conventionally or used as described in the examples .

The compounds of the present invention can be synthesized according to the general reaction scheme and/or the examples described below. The general process can be changed by replacing the starting materials with other materials with similar structures to produce corresponding products. The structure of the desired product will generally make the desired starting material obvious to those skilled in the art.

Schemes 1 and 2 provide exemplary synthetic pathways for the synthesis of the compounds provided herein (eg, compounds of Formula I). The compound of formula I or other chemical formulas or compounds disclosed herein are usually prepared by first providing the core formula X(a) or X(d) and then using suitable conditions (such as coupling) to connect the desired substituents.

In some embodiments, the synthesis of the compound of formula I is carried out according to Scheme 1. Process 1

In process 1, A ¹ , A ² , L, R ¹ , R ⁴ , R ⁵ , X ¹ , X ² and X ³ are as defined in formula I. In Scheme 1, the compound of formula X(a) is converted to the compound of formula X(b) or X(c). Then, the compound of formula X(b) or formula X(c) can be converted into the compound of formula I, respectively.

In Scheme 1, each of Z ¹ , Z ² , Z ³ and Z ⁴ is independently a suitable leaving group, such as a halide or hydroxide (for example, in the presence of triphenylphosphine and dialkyl nitrogen In the case of heterodicarboxylates); suitable coupling partners, such as halides, unitoponates, unitoponates or hydrogen (eg at the terminal alkynes); or suitable electrophiles, such as aldehydes or ketone.

In Scheme 1, R ⁵¹ is R ^5a , hydrogen or a suitable leaving group, such as a halide or hydroxide (for example, in the presence of triphenylphosphine and dialkyl azadicarboxylate), or Suitable coupling partners, such as halides, unitoponates, unitoponates. R ^5a is R ⁵ or a suitable precursor. For example, when R ⁵ contains a carboxylic acid, R ^5a may contain an ester. When R ⁵ contains a carboxylic acid of formula X (b) converted to a formula I or formula X (a) converted to the formula X (c) may comprise the step of hydrolysis of the ester. R ¹⁸ is -LR ¹ , hydrogen or a suitable leaving group, such as halide or hydroxide (for example, in the presence of triphenylphosphine and dialkylazadicarboxylate); suitable coupling partners , Such as halides, phthalic acid, phthalic acid esters; or suitable electrophiles, such as aldehydes or ketones. R ⁴¹ is R ⁴ . Each of A ¹¹ , A ¹² and A ^{13 is A 1} . Each of A ²¹ , A ²² and A ^{23 is A 2} or a part suitable for connecting to A ² , for example, a suitable coupling partner such as a halide, unitoponate, unitoponate, or hydrogen.

Those skilled in the art will understand that for a particular embodiment, any of the compounds of formula X(a), X(b) or X(c) can be obtained from commercial suppliers. Alternative synthesis of compounds of formula X(a), X(b) or X(c) can be as described herein or known to those skilled in the art.

In some embodiments, the synthesis of the compound of formula I is carried out according to Scheme 2. Process 2

In process 2, A ¹ , A ² , L, R ¹ , R ⁴ , R ⁵ , X ¹ , X ² and X ³ are as defined in formula I. In Scheme 1, the compound of formula X(d) is converted to the compound of formula X(e) or X(f). Then, the compound of formula X(e) or formula X(f) can be converted into the compound of formula I, respectively.

In Scheme 2, each of Z ⁵ , Z ⁶ , Z ⁷ and Z ⁸ is independently a suitable leaving group, such as a halide or hydroxide (for example, in the presence of triphenylphosphine and dialkyl nitrogen In the case of heterodicarboxylates); suitable coupling partners, such as halides, unitoponates, unitoponates or hydrogen (eg at the terminal alkynes); or suitable electrophiles, such as aldehydes or ketone.

In Scheme 2, R ⁵² is R ^5b , hydrogen or a suitable leaving group, such as a halide or hydroxide (for example, in the presence of triphenylphosphine and dialkylazadicarboxylate), or Suitable coupling partners, such as halides, unitoponates, unitoponates. R ^5b is R ⁵ or a suitable precursor. For example, when R ⁵ includes a carboxylic acid, R ^5b may include an ester. When R ⁵ contains a carboxylic acid of formula X (e) of formula I or formula is converted into X (d) is converted into formula X (f) may comprise the step of hydrolysis of the ester. R ¹⁹ is -LR ¹ , hydrogen or a suitable leaving group, such as halide or hydroxide (for example, in the presence of triphenylphosphine and dialkyl azadicarboxylate); suitable coupling partners , Such as halides, unitoponates, unitoponates; or suitable electrophiles, such as aldehydes, ketones or nitriles, or α-, β-unsaturated derivatives thereof, or N-protecting groups, such as p-toluenesulfonate An acyl or tertiary butoxycarbonyl group. R ⁴² is R ⁴ or a moiety suitable for connecting R ⁴ , such as hydrogen. Each of A ¹⁴ , A ¹⁵ and A ^{16 is A 1} or a part suitable for connecting A ¹ , for example, a suitable coupling partner such as a halide, unitoponate, unitoponate, or hydrogen. Each of A ²⁴ , A ²⁵ and A ^{26 is A 2} .

Those skilled in the art will understand that for a particular embodiment, any of the compounds of formula X(d), X(e) or X(f) can be obtained from commercial suppliers. Alternative synthesis of compounds of formula X(d), X(e) or X(f) can be as described herein or known to those skilled in the art. Palladium coupling conditions

Where appropriate, when a (hetero)aryl carbon-(hetero)aryl carbon bond is formed, the formula X(a), X(b), X(c), X(d), X(e) or X(f) and compound 501 , 502 , 503 , 504 , 505 , 506 , 507 or 508 are cross-coupling under standard metal-catalyzed conditions (such as using a palladium catalyst) in a suitable solvent (such as dioxane, acetonitrile, Water, etc.), as appropriate, coupling in an inert atmosphere, where Z ¹ , Z ² , Z ³ , Z ⁴ , Z ⁵ , Z ⁶ , Z ⁷ or Z ⁸ are suitable coupling partners, such as halide Compounds or iodides) or unitary acid or its esters. In the presence of a weak base (such as potassium acetate, potassium carbonate, sodium carbonate or sodium bicarbonate) in an inert solvent (such as aqueous 1,4-dioxane or aqueous N,N-dimethylformamide) Carry out a cross-coupling reaction. The reaction is usually carried out on a metal catalyst with suitable ligands, such as dichlorobis(triphenylphosphine)palladium(II) or dichloro 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) In the presence, it is performed at a temperature of about 60°C to 150°C for about 10 minutes to about 12 hours. When the reaction is substantially complete, the product is separated by conventional means. Coupling conditions for copper ("Buchwald")

Where appropriate, for example, when a (hetero)aryl carbon-nitrogen bond is formed, the formula X(a), X(b), X(c), X(d), X(e) or X(f ) And compound 501 , 502 , 503 , 504 , 505 , 506 , 507 or 508 under copper-catalyzed coupling conditions (such as using copper catalyst) in a suitable solvent (such as toluene, DMF, etc.) in an inert atmosphere as appropriate Under coupling, where Z ¹ , Z ² , Z ³ , Z ⁴ , Z ⁵ , Z ⁶ , Z ⁷ or Z ⁸ are suitable coupling partners, such as halides (such as bromides or iodides). In the presence of a weak base (such as potassium carbonate or tripotassium phosphate), the coupling reaction is carried out in an inert solvent (such as toluene or N,N-dimethylformamide). The reaction is usually in the presence of a metal catalyst (such as copper (I) iodide, copper (I) or copper acetate (II) monohydrate), with a suitable ligand (such as reverse N,N'-two Methylcyclohexane-1,2-diamine) at a temperature of about 60 to 150°C for about 10 minutes to about 7 days. When the reaction is substantially complete, the product is separated by conventional means. Aryl nucleophilic replacement conditions

Where appropriate, such as when forming a (hetero)aryl carbon-nitrogen bond, the formula X(a), X(b), X(c), X(d), X(e) or X(f) With compound 501 , 502 , 503 , 504 , 505 , 506 , 507 or 508 under nucleophilic substitution-aromatic ("SN _Ar ") conditions, in a suitable solvent (such as DMSO, DMF, etc.), optionally inert Coupling in an atmosphere, where Z ¹ , Z ² , Z ³ , Z ⁴ , Z ⁵ , Z ⁶ , Z ⁷ or Z ⁸ are suitable leaving groups, such as fluoride. The reaction is carried out in an inert solvent (such as DMSO) in the presence of a weak base (such as potassium carbonate or cesium carbonate). The reaction is usually carried out at a temperature of about 60 to 150°C for about 1 hour to about 7 days. When the reaction is substantially complete, the product is separated by conventional means. Alkynes coupling conditions

Under appropriate circumstances, such as the formation of an alkynyl carbon-nitrogen bond, the formula X(a), X(b), X(c), X(d), X(e) or X(f) and compound 501 , 502 , 503 , 504 , 505 , 506 , 507 or 508 under copper-catalyzed coupling conditions (such as using palladium catalyst and/or copper catalyst), in a suitable solvent (such as toluene, DMF, etc.), as appropriate, inert Coupling in an atmosphere, where Z ¹ , Z ² , Z ³ , Z ⁴ , Z ⁵ , Z ⁶ , Z ⁷ or Z ⁸ are hydrogen or trialkylsilane. The coupling reaction is carried out in an inert solvent (such as toluene or N,N-dimethylformamide) in the presence of a weak base (such as triethylamine). The reaction is usually in the presence of a metal catalyst (such as bis(triphenylphosphine) palladium (II), copper iodide (I) or copper bromide (I)), and a suitable ligand ( For example, reverse N,N'-dimethylcyclohexane-1,2-diamine), at a temperature of about 60 to 150°C for about 10 minutes to about 1 day. When the reaction is substantially complete, the product is separated by conventional means. Ester hydrolysis conditions

Under appropriate circumstances, for example, when ^{the carboxylic acid ester in R 1a} or R ^5a is cleaved to form the carboxylic acid in R ¹ or R ⁵ , respectively, the formula X(a), X(b), X(c), X (D), X(e) or X(f) undergoes ester hydrolysis conditions. The ester hydrolysis conditions may include, for example, the use of a base (such as alkali metal alkoxides (such as sodium methoxide or sodium ethoxide) or alkali metal hydroxides (such as sodium hydroxide or lithium hydroxide)) in a suitable solvent (such as water, In oxane, ethanol and/or THF), the temperature is about 0 to 100°C for about 10 minutes to about 24 hours. When the reaction is substantially complete, the product is separated by conventional means. Instance

The following examples depict general synthetic procedures for the compounds described herein. The synthesis of the compounds described herein is not limited by these examples and procedures. Those skilled in the art will know that other procedures can be used to synthesize the compounds described herein, and the procedures described in the examples and schemes are only one such procedure. In the following description, those skilled in the art will recognize that specific reaction conditions, added reagents, solvents, and reaction temperature can be modified to synthesize specific compounds within the scope of the present invention. Unless otherwise specified, the intermediate compounds described in the following examples (without instructions on how to prepare the intermediate compounds) are commercially available to those skilled in the art or can be used by those skilled in the art. Commercially available precursor molecules and synthetic methods known in the art are synthesized in other ways.

The following schemes and synthesis examples are intended to be illustrative and do not limit or limit the scope of the invention. Example 1

Step 1 : Preparation of 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1-( phenylsulfonyl )-1H- pyrrolo [2,3-b] pyridine -3 - yl) pyridine-2-carboxylate: to a solution containing 4- [1- (benzenesulfonyl acyl) -3-iodo-yl - pyrrolo [2,3-b] pyridin-5-yl] -3,5- Methyl-isoxazole ( 1 , 150 mg, 0.313 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxoboro-2-yl)pyridine-2 -Methyl formate (167 mg, 0.635 mmol) 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (26.6 mg, 0.033 mmol) by microwave Add 1,4-dioxane (3 ml) to the pressure vial. The flask was purged with argon and hydrogen and then 2.5 M aqueous potassium carbonate (0.376 ml) was added. The vial was sealed and stirred in an oil bath at 120°C for 2 hours. The reaction was cooled to room temperature and the two-phase mixture was filtered through Celite, washing with THF and ethyl acetate. The filtrate was concentrated under reduced pressure and dissolved with a gradient of 0-100% ethyl acetate/hexane, and the substance was purified by silica gel flash column chromatography. This produces 4-(5-(3,5-dimethylisoxazol-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl ) Methyl picolinate ( 2 ). MS (ESI) [M+H ⁺ ] ⁺ = 489.0.

Step 2 : Preparation of 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1-( phenylsulfonyl )-1H- pyrrolo [2,3-b] pyridine -3 - yl) picolinic acid P-0055: in an ice bath dissolved in dioxane (6 ml) of the 4- (5- (3,5-dimethyl-4-yl) -1- ( A solution of methyl phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinate ( 2 , 78.5 mg, 0.16 mmol) was cooled. Next, add 3 ml of 1 M LiOH (aqueous). After 30 minutes, the reaction was quenched with 1 M HCl (aqueous) to pH 1 and then extracted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The volatiles were removed by rotary evaporation and by reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) to obtain 4-(5-(3,5-dimethylisoxazol-4-yl)-1-(phenylsulfonyl )-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinic acid ( P-0055 ). MS (ESI) [M+H ⁺ ] ⁺ = 474.9. Example 2

Step 1 : Preparation of 4-(3- iodo- 1 -tosyl- 1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxazole 4 : To Packed with 4-(3-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethyl-isoxazole ( 3 , 10 g, 29.5 mmol) and anhydrous Sodium hydride (60%, 1.65 g, 41.3 mmol) was added to a round bottom flask of THF (150 ml). The reaction was stirred at room temperature for 1 hour, then 4-methylbenzenesulfonyl chloride (6.80 g, 35.7 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with brine (160 mL) and diluted with ethyl acetate (160 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dry loaded onto silica gel and eluted with 0-20% ethyl acetate/hexane and purified by silica gel flash column chromatography to obtain 4-(3-iodo-1-tosyl-1H-pyrrole And [2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 4 ). MS (ESI) [M+H ⁺ ] ⁺ = 493.9.

Step 2 : Preparation of 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1 -toluenesulfonyl- 1H- pyrrolo [2,3-b] pyridin- 3 -yl ) -2,2 -Dimethylbutan- 3- acid methyl ester 5 : Purge 4-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-5 with nitrogen - yl) -3,5-dimethyl-isoxazole (4, 104 mg, 0.21 mmol ), bis (triphenylphosphine) palladium (II) dichloride (4.42 mg, 6.3 μmol) and copper iodide ( I) (1.2 mg, 6.3 μmol) in a mixture of triethylamine-containing acetonitrile (2.0 ml) (1:3), followed by the addition of methyl 2,2-dimethylbutanoate (53 mg, 0.42 mmol). The mixture was heated at 90°C for 2 hours. The mixture was concentrated under reduced pressure and purified by flash chromatography with 20% ethyl acetate/hexane to obtain 4-(5-(3,5-dimethylisoxazol-4-yl)-1-toluene Sulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2-dimethylbut-3-acid methyl ester ( 5 ). MS (ESI) [M+H ⁺ ] ⁺ = 492.2.

Step 3 : Preparation of 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3-b] pyridin- 3 -yl )-2,2 -dimethyl Methylbutan- 3- acid 6 : To 4-(5-(3,5-dimethylisoxazol-4-yl)-1-toluenesulfonyl-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-2,2-dimethylbutan-3-acid methyl ester ( 5 , 88 mg, 0.18 mmol) in THF (2 ml) was added to a mixture of 1 M TBAF in THF (0.400 ml). The mixture was stirred at 70°C for 15 hours. The reaction was diluted with ethyl acetate and washed successively with saturated sodium bicarbonate (aqueous), water and brine. The layers were separated and the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure and wet triturated with 5% ethyl acetate/hexane to give 4-(5-(3,5-dimethylisoxazole-4 -Yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2-dimethylbut-3-acid methyl ester ( 6 ). MS (ESI) [M+H ⁺ ] ⁺ = 338.6.

Step 4 : Preparation of 4-(1- benzyl- 5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3-b] pyridin- 3 -yl )- 2,2 -Dimethylbutan- 3- acid methyl ester 7 : To 4-(5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] Pyridin-3-yl)-2,2-dimethylbutan-3-acid methyl ester ( 6 , 28.6 mg) in DMF (1 ml) is added 60% NaH/mineral oil (60%, 4.07 mg , 0.1 mmol). The mixture was stirred for 2 minutes and then bromomethylbenzene (21.75 mg, 0.13 mmol) was added. The resulting mixture was stirred at 60°C for 2 hours. The mixture was diluted with water, extracted with ethyl acetate, and the organic layer was washed successively with water and brine. The layers were separated and the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The material was purified by flash chromatography by eluting with 50% ethyl acetate/hexane to obtain 4-(1-benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrole And [2,3-b]pyridin-3-yl)-2,2-dimethylbut-3-acid methyl ester ( 7 ). MS (ESI) [M+H ⁺ ] ⁺ = 428.6.

Step 5 : Preparation of 4-(1- benzyl- 5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3-b] pyridin- 3 -yl )- 2,2 -Dimethylbut- 3- ynoic acid P-0051 : To 4-(1-benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo [2,3-b]pyridin-3-yl)-2,2-dimethylbutan-3-acid methyl ester ( 7 , 22.6 mg, 0.05 mmol) in (1:1) THF/MeOH (0.5 ml) Add 4.18 M LiOH (0.030 ml) to the mixture. The mixture was stirred at 70°C for 3 hours. The reaction was acidified with MeOH containing 3 N HCl and concentrated under reduced pressure. By reverse phase HPLC (C18; 0-100% B;, A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1 % HCO ₂ H) to purify the material to obtain 4-(1-benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-2,2-dimethylbut-3-ynoic acid ( P-0051 ). MS (ESI) [M+H ⁺ ] ⁺ = 414.5. Example 3

Step 1 : Preparation of (S)-4-(3- iodo- 1-(1-( pyridin -2- yl ) ethyl )-1H- pyrrolo [3,2-b] pyridin -6- yl )- 3,5 -Dimethylisoxazole 9 : To contain 4-(3-iodo-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxazole ( 8 , 0.92 g, 2.71 mmol) in THF (20 ml) were added (1R)-1-(2-pyridyl)ethanol (0.38 g, 3.09 mmol) and triphenylphosphine (0.957 g, 3.65 mmol) successively . The reaction was cooled to 0°C in an ice water bath, and then diisopropyl azodicarboxylate (0.738 g, 3.65 mmol) was added dropwise. After 1 hour, the reaction was removed from the ice bath and warmed to room temperature for 1 hour. The reactant was concentrated under reduced pressure and purified by silica gel column chromatography with 20% to 100% ethyl acetate/hexane to obtain (S)-4-(3-iodo-1-(1-(pyridine) -2-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxazole ( 9 ).

Step 2 : Preparation of (S)-4-(3- iodo- 1-(1-( pyridin -2- yl ) ethyl )-2-( trifluoromethyl )-1H- pyrrolo [3,2- b] Pyridin -6- yl )-3,5 -dimethylisoxazole 10 : To (S)-4-(3-iodo-1-(1-(pyridin-2-yl)ethyl)- 1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxazole ( 9 , 0.91 g, 2.05 mmol) and zinc trifluoromethanesulfinate (1.36 g, 4.10 mmol) was added DMSO (10 ml) and water (4 ml) successively. The reaction was cooled in an ice bath and t-butyl hydroperoxide (0.86 ml, 6.8 mmol) was added dropwise. The reaction was removed from the ice bath and warmed to ambient temperature, and then placed in an oil bath at 50°C and stirred overnight. After 22 hours, LCMS indicated about 10% product formation. Add another 1.27 g of zinc trifluoromethanesulfinate, followed by 1 ml of tertiary butyl hydroperoxide. The reaction was allowed to continue for another 17 hours at 50°C. The reaction was extracted with saturated sodium bicarbonate and ethyl acetate. The organic layer was separated and the aqueous layer was extracted 3 more times with 5 mL portions of ethyl acetate. The organic layers were combined and the volatiles were removed by rotary evaporation to obtain a crude product, which was purified by silica gel column chromatography (10-60% ethyl acetate/hexane). This produces (S)-4-(3-iodo-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl)-1H-pyrrolo[3,2-b] Pyridin-6-yl)-3,5-dimethylisoxazole ( 10 ). MS (ESI) [M+H ⁺ ] ⁺ = 512.1.

Step 3 : Preparation of (S)-3,5 -dimethyl- 4-(3-(1 -methyl -1H- pyrazol- 4 -yl )-1-(1-( pyridin -2- yl ) ethyl yl) -2- (trifluoromethyl) lH-pyrrolo [3,2-b] pyridin-6-yl) isoxazol-P-160: equipped containing (S) -4- (3- iodo Base-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-di Methylisoxazole ( 10 , 61.47 mg, 0.12 mmol), 1-methyl-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaboron-2-yl ) Pyrazole (49.94 mg, 0.24 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (9.8 mg, 0.012 mmol) _{Add 2.5 M aqueous K 2} CO ₃ (0.144 ml) to a reaction flask purged with oxane (2 ml) and nitrogen. The mixture was heated at 110°C for 15 hours. The sample was diluted with ethyl acetate and dried over anhydrous magnesium sulfate; filtered, concentrated and eluted with 100% ethyl acetate to purify by flash chromatography, followed by reverse phase chromatography to obtain (S)-3,5-dimethyl -4-(3-(1-methyl-1H-pyrazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl)-1H-pyrrole And [3,2-b]pyridin-6-yl)isoxazole ( P-0160 ). MS (ESI) [M+H ⁺ ] ⁺ = 467.6 Example 4

Step 1 : Preparation of (3-( benzyloxy ) phenyl )(6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b] pyridine -3 - yl) methanol 12: to a solution of 3,5-dimethyl -4- (1H- pyrrolo [3,2-b] pyridin-6-yl) isoxazole (11 .0.24 g.1.11 mmol) of methanol (5 ml) potassium hydroxide (0.177 g, 3.15 mmol) and 3-benzyloxybenzaldehyde (0.26 g, 1.23 mmol) were added. The mixture was stirred at room temperature for 4 hours. The reaction mixture was extracted with ethyl acetate and water with 1 N citric acid. The organic layer was washed with water and brine, then dried over magnesium sulfate and filtered. The volatiles were removed under reduced pressure and the material was purified by silica gel column chromatography (0-60% ethyl acetate/hexane). This produces (3-(benzyloxy)phenyl)(6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl ) Methanol ( 12 ). MS (ESI) [M+H ⁺ ] ⁺ = 426.5.

Step 2 : Preparation of (3-( benzyloxy ) phenyl )(6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b] pyridine -3 - yl) methanone 13: to a solution of (3- (benzyloxy) phenyl) (6- (3,5-dimethyl-4-yl) lH-pyrrole provided and [3 ,2-b]Pyridin-3-yl)methanol ( 12 , 34 mg, 0.080 mmol) in tetrahydrofuran (10 ml) was added Dess-Martin periodinane (0.07 g, 0.16 mmol). The mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate and filtered. The volatiles were removed under reduced pressure and the material was purified by silica gel column chromatography (0-100% ethyl acetate/dichloromethane) to obtain (3-(benzyloxy)phenyl)(6-(3) ,5-Dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl)methanone ( 13 ). MS (ESI) [M+H ⁺ ] ⁺ = 424.1.

Step 3 : Preparation of 4-(3-(3-( benzyloxy ) benzyl )-6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3, 2-b] pyridin- 1 -yl )-3,5- dichlorobenzoic acid P-0133 : to (3-(benzyloxy)phenyl)(6-(3,5-dimethylisoxazole) -4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl)methanone ( 13 , 29 mg, 0.068 mmol), 3,5-dichloro-4-fluoro-benzoic acid (40 DMSO (3 ml) was added to the mixture of mg, 0.19 mmol) and cesium carbonate (120 mg, 0.37 mmol). The reaction mixture was heated at 90°C for 3 days. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate and filtered. The volatiles were removed under reduced pressure and by reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN , 5% H ₂ O, 0.1% HCO ₂ H) to purify the crude material to obtain 4-(3-(3-(benzyloxy)benzyl)-6-(3,5-dimethylisoxan (Azol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-dichlorobenzoic acid ( P-0133 ). MS (ESI) [M+H ⁺ ] ⁺ = 612.0. Example 5

Step 1 : Preparation of 4-(6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b] pyridin- 1 -yl )-3,5- diethyl Ethyl oxybenzoate 14 : Combine 3,5-dimethyl-4-(1H-pyrrolo[3,2-b]pyridin-6-yl)isoxazole ( 11 , 0.60 g, 2.81 mmol), ethyl 4-bromo-3,5-diethoxybenzoate (1.34 g, 4.21 mmol), tripotassium phosphate (1.25 g, 5.91 mmol), copper (I) iodide (0.11 g, 0.56 mmol), trans N,N'-dimethylcyclohexane-1,2-diamine (0.80 g, 5.6 mmol) and purged with argon. The reaction mixture was stirred at 110°C overnight. The reaction mixture was cooled to ambient temperature, diluted with 2 mL of ethyl acetate and filtered through a pad of celite with ethyl acetate. This material was purified by silica gel column chromatography (0-50% ethyl acetate/hexane) to obtain 4-(6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo [3,2-b]pyridin-1-yl)-3,5-diethoxy ethyl benzoate ( 14 ).

Step 2 : Preparation of 4-(3- bromo -6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b] pyridin- 1 -yl )-3, Ethyl 5 -diethoxybenzoate 15 : Add 4-(6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2 -b] pyridin-1-yl) -3,5-ethoxy ethyl benzoate (14, 620 mg, 1.38 mmol ) , and acetonitrile (14 mL). The reaction flask was placed under N ₂ and cooled to 0° C., then N-bromosuccinimide (246 mg, 1.38 mmol) was added slowly. The reaction mixture was stirred at 0°C and warmed to room temperature for 2 hours. The reaction was diluted with ethyl acetate and partitioned between water and ethyl acetate. The extracted organic portion was washed with brine and dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (0-60% ethyl acetate/hexane) to obtain 4-(3-bromo-6-(3,5-dimethylisoxazole- 4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxy ethyl benzoate ( 15 ).

Step 3 : Preparation of 4-(3-(4-( cyclopropylaminocarboxyl ) phenyl )-6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3 ,2-b] pyridin- 1 -yl )-3,5 -diethoxybenzoic acid P-0218 : Combine 4-(3-bromo-6-(3) in dioxane/acetonitrile (0.5 ml each) ,5-Dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid ethyl ester ( 15 , 40 mg , 0.08 mmol), (4-(cyclopropylaminomethanoyl)phenyl) unitoponic acid (31 mg, 0.15 mmol), 1,1'-bis(diphenylphosphino)ferrocene-dichloro Palladium(II) dichloromethane complex (8.7 mg, 0.011 mmol) and 2.5 M aqueous K ₂ CO ₃ (0.09 ml) were heated to 100° C. for 8 hours. Then the reaction was cooled, filtered through celite and purified by silica gel column chromatography (0-10% methanol/dichloromethane) to obtain 4-(3-(4-(cyclopropylaminomethanyl)benzene) Yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid ( P-0218 ). MS (ESI) [M+H ⁺ ] ⁺ = 581.2. Example 6

Step 1 : Preparation of (S)-5- bromo- 1-(1-( pyridin -2- yl ) ethyl )-1H- pyrrolo [2,3-b] pyridine 17 : under nitrogen, to ice-cold 5 - bromo -1H- pyrrolo [2,3-b] pyridine (16, 689 mg, 3.5 mmol ), (1R) -1- (2- pyridyl) ethanol (646 mg, 5.25 mmol), and triphenylphosphine (1377 mg, 5.25 mmol) in THF (35 ml) was slowly added diisopropyl azodicarboxylate (1.04 ml, 5.25 mmol). The mixture was stirred and allowed to reach room temperature for 15 hours. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography by eluting with 20% ethyl acetate/hexane to obtain (S)-5-bromo-1-(1-(pyridin-2-yl)ethyl) -1H-pyrrolo[2,3-b]pyridine ( 17 ). MS (ESI) [M+H ⁺ ] ⁺ = 303.9.

Step 2 : Preparation of (S)-3,5 -dimethyl- 4-(1-(1-( pyridin -2- yl ) ethyl )-1H- pyrrolo [2,3-b] pyridine -5- yl) isoxazole 18: purged with nitrogen (S) -5- bromo-1- (1- (pyridin-2-yl) ethyl) lH-pyrrolo [2,3-b] pyridine (17, 618 mg, 2.05 mmol), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoborodon-2-yl)isoxazole ( 502 mg, 2.25 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (149 mg, 0.182 mmol) in dioxane (20 ml), then add 2.5 MK ₂ CO ₃ (2.5 ml). The mixture was heated at 100°C for 4 hours. The sample was diluted with ethyl acetate and dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The substance was purified by silica gel column chromatography by elution with 40% ethyl acetate/hexane to obtain (S)-3,5-dimethyl-4-(1-(1-(pyridin-2-yl)ethyl) )-1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole ( 18 ). MS (ESI) [M+H ⁺ ] ⁺ = 319.5.

Step 3 : Preparation of (S)-4-(3- iodo- 1-(1-( pyridin -2- yl ) ethyl )-1H- pyrrolo [2,3-b] pyridin -5- yl )- 3,5 -Dimethylisoxazole 19 : To the ice-cold (S)-3,5-dimethyl-4-(1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo [2,3-b] pyridin-5-yl) isoxazole (18, 620 mg, 1.56 mmol ) in acetonitrile (20 ml) was added in the iodine-butylene N- (PEI) (420 mg, 1.87 mmol ). The mixture was stirred to reach room temperature for 2 hours. The mixture was diluted with saturated _{aqueous Na 2} S ₂ O ₃ solution, extracted with ethyl acetate and the organic layer was washed with water and successively. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The substance was purified by silica gel column chromatography by elution with 40% ethyl acetate/hexane to obtain (S)-4-(3-iodo-1-(1-(pyridin-2-yl)ethyl)-1H -Pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 19 ). MS (ESI) [M+H ⁺ ] ⁺ = 445.0.

Step 4 : Preparation of methyl 4- bromo- 3-( cyclopropylethynyl ) benzoate 21 : Purge methyl 4-bromo-3-iodo-benzoate ( 20 , 1022 mg, 3 mmol) with nitrogen, Bis(triphenylphosphine) palladium(II) dichloride (63 mg, 0.09 mmol) and copper(I) iodide (17 mg, 0.09 mmol) in acetonitrile (20.0 ml) containing triethylamine (1:3) ), then add ethynylcyclopropane (238 mg, 3.6 mmol). The mixture was heated at 60°C for 5 hours. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography by eluting with 30% dichloromethane/hexane to obtain methyl 4-bromo-3-(cyclopropylethynyl)benzoate ( 21 ). MS (ESI) [M+H ⁺ ] ⁺ = 280.9.

Step 5: Preparation of 3- (cyclopropylmethoxy) -4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan Mouth 2-yl) benzoate 22 : Heat 4-bromo-3-(cyclopropylethynyl) methyl benzoate ( 21 , 307 mg, 1.1 mmol), bis(pinacolyl) diboron (419 mg, 1.65 mmol) at 100°C, 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (89.83 mg, 0.104 mmol) and potassium acetate (323 mg, 3.3 mmol) in dioxins Mixture in alkane (10 ml) for 15 hours. The mixture was diluted with ethyl acetate, washed with water, brine, and dried over anhydrous magnesium sulfate. The organic layer was filtered and concentrated under reduced pressure. The sample was purified by silica gel column chromatography with 10% ethyl acetate/hexane to obtain 3-(cyclopropylethynyl)-4-(4,4,5,5-tetramethyl-1,3, 2-Dioxoboron-2-yl)methyl benzoate ( 22 ). MS (ESI) [M+H ⁺ ] ⁺ = 327.1.

Step 6 : Preparation of (S)-3-( cyclopropylethynyl )-4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1-(1-( pyridine -2- yl) ethyl) lH-pyrrolo [2,3-b] pyridin-3-yl) benzoic acid methyl ester 23: to a solution of (S) -4- (3- iodo-1- (1- (pyridin- -2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 19 , 62 mg, 0.14 mmol), 3-( 2-Cyclopropylethynyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)methyl benzoate ( 22 , 150 mg, 0.46 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (11.43 mg, 0.013 mmol) in dioxane (2 ml) Add 2.5 MK ₂ CO ₃ (0.170 ml). The mixture was heated at 100°C for 4 hours. The sample was diluted with ethyl acetate, washed successively with water and brine, and dried over anhydrous magnesium sulfate. The organic layer was filtered and concentrated under reduced pressure. The substance was purified by silica gel column chromatography by elution with 50% ethyl acetate/hexane to obtain (S)-3-(cyclopropylethynyl)-4-(5-(3,5-dimethylisoxan) (Azol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid methyl ester ( 23 ). MS (ESI) [M+H ⁺ ] ⁺ = 517.2.

Step 7 : Preparation of (S)-3-( cyclopropylethynyl )-4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1-(1-( pyridine -2- yl) ethyl) lH-pyrrolo [2,3-b] pyridin-3-yl) benzoic acid P-0178: the (S) -3- (cyclopropylmethyl) -4- (5- ( 3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzene To a mixture of methyl formate ( 23 , 12 mg, 0.02 mmol) in (1:1) THF/MeOH (1 ml) was added aqueous 4.18 M LiOH (0.020 ml). The mixture was stirred at 70°C for 3 hours. The mixture was acidified with 3 M HCl/MeOH, diluted with ethyl acetate and concentrated under reduced pressure. By reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) Purify the material to obtain (S)-3-(cyclopropylethynyl)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-( Pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid ( P-0178 ). MS (ESI) [M+H ⁺ ] ⁺ = 503.2. Example 7

Step 1 : Preparation of methyl 4-(4,4,5,5 -tetramethyl -1,3,2- dioxaborodon -2- yl )-3-( trifluoromethoxy ) benzoate 25 : Heat 4-bromo-3-(trifluoromethoxy)methyl benzoate (344 mg, 1.15 mmol), bis(pinacol radical) diboron ( 24 , 584 mg, 2.3 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (94 mg, 0.115 mmol) and potassium acetate (339 mg, 3.45 mmol) in dioxins Mixture in alkane (12 ml) for 15 hours. The mixture was diluted with ethyl acetate, washed with water and brine, and then dried over anhydrous magnesium sulfate. The organic layer was filtered and concentrated under reduced pressure. The material was purified by silica gel column chromatography by elution with 10% ethyl acetate/hexane to obtain 4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2- Methyl)-3-(trifluoromethoxy)benzoate ( 25 ). MS (ESI) [M+H ⁺ ] ⁺ = 347.1.

Step 2 : Preparation of 4-(1-((1- cyanocyclobutyl ) methyl )-5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3 -b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid methyl ester 27 : To the 1-((5-(3,5-dimethylisoxazole-4) purged with nitrogen -Yl)-3-iodo-1H-pyrrolo[2,3-b]pyridin-1-yl)methyl)cyclobutane-1-carbonitrile ( 26 , 52 mg, 0.12 mmol, with compound 19 Prepared in a similar way), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)-3-(trifluoromethoxy)benzoic acid methyl Ester ( 25 , 54 mg, 0.16 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (9.8 mg, 0.012 mmol) in two Add aqueous 2.5 M potassium carbonate (0.150 ml) to the mixture in oxane (2 ml). The mixture was heated at 110°C for 3 hours. The sample was diluted with ethyl acetate and dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The substance was purified by silica gel column chromatography by elution with 40% ethyl acetate/hexane to obtain 4-(1-((1-cyanocyclobutyl)methyl)-5-(3,5-dimethyl) Isoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 27 ). MS (ESI) [M+H ⁺ ] ⁺ = 525.1.

Step 3 : Preparation of 4-(1-((1- cyanocyclobutyl ) methyl )-5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3 -b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid P-0364 : To contain 4-(1-((1-cyanocyclobutyl)methyl)-5-(3 , 5-dimethyl-isoxazol-4-yl) lH-pyrrolo [2,3-b] pyridin-3-yl) -3- (trifluoromethoxy) benzoate (27, 31 mg, 0.06 mmol) (1:1) THF/MeOH (2.0 ml) was added aqueous 4.18 M LiOH (0.050 ml). The mixture was stirred at 70°C for 2 hours. The mixture was diluted with ethyl acetate, acidified with MeOH containing 1 N HCl and concentrated under reduced pressure. By reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) Purify the material to obtain 4-(1-((1-cyanocyclobutyl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo [2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid ( P-0364 ). MS (ESI) [M+H ⁺ ] ⁺ = 511.2. Example 8

Step 1 : Preparation of methyl 4- ethoxypicolinate 29 : Stirring methyl 4-hydroxypyridine-2-carboxylate hydrochloride ( 28 , 3.79 g, 20.00 mmol), iodoethane (2.41 ml, 30.00 mmol), potassium carbonate (8.29 g, 60.00 mmol) and N,N-dimethylformamide (60 mL) mixture overnight. The reaction mixture was poured into water (200 mL) and extracted with ethyl acetate/hexane=1/1 (600 mL). The organic layer was separated, washed with water (2×100 mL), brine (100 mL), dried over anhydrous sodium sulfate, filtered through a short silica gel pad and concentrated under reduced pressure. This produces methyl 4-ethoxypicolinate ( 29 ).

Step 2 : Preparation of 1- oxy 4- ethoxy -2-( methoxycarbonyl ) pyridine 30 : Add methyl 4-ethoxypicolinate ( 29 , 2.53 g, 13.96 mmol) in acetic acid at 0°C To the solution in ethyl ester (40.0 mL), mCPBA (77%, 3.755 g, 16.76 mmol) was added portionwise and stirred at room temperature for 22 hours. Additional mCPBA (77%, 1.876 g, 8.38 mmol) was added and the mixture was stirred for another 5 hours. The reaction was diluted with ethyl acetate (200 mL) and washed with saturated aqueous sodium bicarbonate (50 mL). The separated aqueous phase was extracted with DCM/MeOH=9/1 (5×50 mL) and the combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (0-10% methanol/dichloromethane) to obtain 1-oxide 4-ethoxy-2-(methoxycarbonyl)pyridine ( 30 ).

Step 3: Preparation of 4-ethoxy-6-hydroxy-pyridine-carboxylic acid methyl ester 31: at 0 deg.] C, over 5 minutes to 4-ethoxy-1 -oxy-2- (methoxycarbonyl) pyridine (30, 740 mg, 3.75 mmol) and triethylamine (1.57 mL, 11.26 mmol) in THF (20.0 mL) was added dropwise trifluoroacetic anhydride (1.57 mL, 11.86 mmol). The mixture was stirred for another 4 hours at 0°C. The reaction was diluted with dichloromethane (200 mL) and extracted with a mixed solution of saturated aqueous sodium bicarbonate (10 mL) and brine (50 mL). The organic layer was separated and dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude material obtained was purified by silica gel column chromatography (0-10% methanol/dichloromethane) to obtain methyl 4-ethoxy-6-hydroxypicolinate ( 31 ). MS (ESI) [M+H ⁺ ] ⁺ = 198.1.

Step 4 : Preparation of methyl 4,6 -diethoxypicolinate 32 : To methyl 4-ethoxy-6-hydroxypicolinate ( 31 , 313 mg, 1.59 mmol), potassium carbonate (329 mg, 2.38 mmol) ) To the mixture in DMF (8 mL) was added ethyl iodide (0.255 mL, 3.18 mmol) and the mixture was stirred at room temperature overnight. The reaction was diluted with ethyl acetate/hexane (1/1, 150 ml) and extracted with water (50 ml, 3 times) and brine (30 ml). The organic layer was dried over anhydrous sodium sulfate, filtered through a short silica gel pad and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (0-20% ethyl acetate/hexane) to obtain methyl 4,6-diethoxypicolinate ( 32 ).

Step 5 : Preparation of methyl 5- bromo -4,6 -diethoxypicolinate 33 : Add methyl 4,6-diethoxypicolinate ( 32 , 95 mg, 0.42 mmol) in DMF (1.5 ml) To the solution in N-bromosuccinimide (76 mg, 0.43 mmol) was added and the mixture was stirred at 50°C overnight. Add another 2 equivalents of N-bromosuccinimide (15 mg, 0.18 mmol) and stir for another 1 hour. LC/MS indicated that the reaction was incomplete, so another 2 equivalents of N-bromosuccinimide (15 mg, 0.18 mmol) were added and stirred for another 1 hour. LC/MS confirmed that all starting material was consumed and the conversion was complete. The reaction was diluted with ethyl acetate/hexane (1/1, 20 mL) and extracted with 5% aqueous sodium thiosulfate (3 mL), water (5 mL), and brine (5 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The material was purified by silica gel column chromatography (0-15% ethyl acetate/hexane) to obtain methyl 5-bromo-4,6-diethoxypicolinate ( 33 ).

Step 6 : Preparation of 4-(1-(2,4 -difluorophenyl )-1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxazole 35 : Stir 3,5-dimethyl-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole ( 34 , 2.13 g, 10.00 mmol), 2,4-dimethyl-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole (34, 2.13 g, 10.00 mmol) at 110°C Bromodifluorobenzene (3.39 mL, 30.00 mmol), potassium carbonate (6.91 g, 50.00 mmol), CuI (571 mg, 3.00 mmol), trans N,N'-dimethylcyclohexane-1,2-diamine (0.473 mL, 3.00 mmol) in toluene (100 mL) for 7 hours. Additional 2,4-difluorobromobenzene (2.26 mL, 20.00 mmol) was added and the reaction continued overnight. The reaction mixture was filtered through Celite and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (0-50% ethyl acetate/hexane) to obtain 4-(1-(2,4-difluorophenyl)-1H-pyrrolo[ 2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 35 ).

Step 7 : Preparation of 4-(3- bromo- 1-(2,4 -difluorophenyl )-1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethyliso Oxazole 36 : At 0 ℃, to 4-(1-(2,4-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethyl Add N-bromosuccinimide (1.49 g, 8.35 mmol) to a solution of oxyisoxazole ( 35, 2.47 g, 7.59 mmol) in acetonitrile (75 ml). The reaction was stirred at 0°C for 30 minutes and then at room temperature for 20 minutes, followed by the addition of aqueous 5% sodium thiosulfate (20 ml). The reactant was concentrated under reduced pressure to remove acetonitrile and then saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine (50 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The material was purified by silica gel column chromatography (0-20% ethyl acetate/hexane) to obtain 4-(3-bromo-1-(2,4-difluorophenyl)-1H-pyrrolo[2, 3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 36 ).

Step 8 : Preparation of 4-(1-(2,4 -difluorophenyl )-3-(4,4,5,5 -tetramethyl -1,3,2- dioxaborodon -2- yl )-1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxazole 37 : Stir 4-(3-bromo-1 at 95°C under a nitrogen atmosphere -(2,4-Difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 36 , 1.68 g, 4.15 mmol), Bis(pinacol radical) diboron (2.11 g, 8.30 mmol), X-Phos (119 mg, 0.249 mmol), Pd2dba3 (114 mg, 0.125 mmol), potassium acetate (1631 mg, 16.62 mmol) and toluene (40 mL) of the mixture for 8 hours. The reaction was filtered through celite and concentrated under reduced pressure. The mixture was purified by silica gel column chromatography (0-10% ethyl acetate/dichloromethane) to obtain 4-(1-(2,4-difluorophenyl)-3-(4,4,5,5) -Tetramethyl-1,3,2-dioxoboron-2-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 37 ).

Step 9 : Preparation of 5-(1-(2,4 -difluorophenyl )-5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3-b] Pyridin- 3 -yl )-4,6 -diethoxypicolinic acid P-0329 : Stir 4-(1-(2,4-difluorophenyl)-3-(4,4,5) at 95°C ,5-Tetramethyl-1,3,2-dioxoboron-2-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethyliso Oxazole ( 37 , 57 mg, 0.095 mmol), methyl 5--4,6-diethoxypicolinate ( 33 , 29 mg, 0.095 mmol), Pd(OAc) ₂ (1.1 mg, 0.005 mmol), S-Phos (2.0 mg, 0.005 mmol), potassium phosphate (61 mg, 0.286 mmol), 1,4-dioxane (1 ml) and water (0.2 ml) for 4 hours. Then, aqueous 1 N HCl (1 ml) was added and the mixture was diluted with dichloromethane/methanol (10/1, 20 ml) and filtered through Celite. The mother liquor was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude material obtained was purified by silica gel column chromatography (0-10% methanol/dichloromethane) to obtain the methyl ester of P-0329 (85 mg). This material was dissolved in THF (0.75 ml) and methanol (0.25 ml) and 2N LiOH aqueous solution (0.25 ml) was added to the solution, and the resulting mixture was stirred at room temperature for 2 hours. After adding aqueous 1 N HCl (0.25 ml), the mixture was concentrated under reduced pressure and purified by silica gel column chromatography (0-10% methanol/dichloromethane) to give 5-(1-(2,4- Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-4,6-diethoxy Picolinic acid ( P-0329 ). MS (ESI) [M+H ⁺ ] ⁺ = 535.2. Example 9

Step 1 : Preparation of methyl 4- amino- 3 -chloro -5-( trifluoromethoxy ) benzoate 39 : To methyl 4-amino-3-(trifluoromethoxy)benzoate ( 38 , 1.06 g, 4.5 mmol) in acetonitrile (40 ml) was added N-chlorosuccinimide (631 mg, 4.73 mmol). The mixture was heated at 80°C for 3 hours. The reaction was diluted with saturated aqueous sodium thiosulfate solution and extracted with ethyl acetate, washed successively with water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain methyl 4-amino-3-chloro-5-(trifluoromethoxy)benzoate ( 39 ). MS (ESI) [M+H ⁺ ] ⁺ = 270.0.

Step 2 : Preparation of 4- bromo- 3 -chloro -5-( trifluoromethoxy ) benzoic acid methyl ester 40 : at 0℃, to 4-amino-3-chloro-5-(trifluoromethoxy) ) Sodium nitrite (193 mg, 2.79 mmol) is slowly added to a mixture of methyl benzoate ( 39, 502 mg, 1.86 mmol) in aqueous HBr (10 ml). The mixture was stirred at 0°C for 10 minutes, then copper(I) bromide (294 mg, 2.05 mmol) was added. The mixture was allowed to warm to room temperature over 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The material was purified by silica gel column chromatography (20% dichloromethane/hexane) to obtain methyl 4-bromo-3-chloro-5-(trifluoromethoxy)benzoate ( 40 ).

Step 3 : Preparation of 4-(3- iodo- 1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5- Dimethylisoxazole 41 : at -20℃, to 4-(3-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole Azole ( 3 , 4.4 g, 12.97 mmol, 1 equivalent), tetrahydro-2H-piperan-4-ol (1.99 g, 19.5 mmol, 1.5 equivalents) and triphenylphosphine (5.10 g, 19.46 mmol, 1.5 equivalents) To the solution in THF (65 mL), add 1 M diisopropyl azodicarboxylate in THF (19.46 mL, 19.46 mmol, 1.5 equivalents) dropwise. The reaction was warmed to room temperature and stirred overnight. The volatiles were removed under reduced pressure and the residue was wet-milled with toluene (about 100 mL) and filtered to give 4-(3-iodo-1-(tetrahydro-2H-piperan-4-yl)-1H- Pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 41 ).

Step 4 : Preparation of 3,5 -dimethyl- 4-(1-( tetrahydro -2H -piperan- 4 -yl )-3-(4,4,5,5 -tetramethyl- 1,3, 2- Dioxoboron -2- yl )-1H- pyrrolo [2,3-b] pyridin -5- yl ) isoxazole 42 : at 0℃, to 4-(3-iodo-1 -(Tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 41 , 3.2 g, 7.56 mmol, 1 equivalent) To a slurry in THF (76 mL) was added 2 M isopropylmagnesium chloride (9.1 mL, 18.15 mmol, 2.4 equivalents) in THF. The reaction was warmed to room temperature and stirred for 30 minutes to cause dissolution, at which time the metal/halogen exchange was completed by 1H NMR measurement. The solution was cooled to 0°C and pinacol borane (3.29 mL, 22.68 mmol, 3 equivalents) was added. The reaction was warmed to room temperature and stirred overnight. The reaction was poured into saturated ammonium chloride (200 mL) and extracted with ethyl acetate (200 mL). The organic layer was washed with saturated brine (200 mL) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0 to 100% ethyl acetate/heptane). This produces 3,5-dimethyl-4-(1-(tetrahydro-2H-piperan-4-yl)-3-(4,4,5,5-tetramethyl-1,3,2- Dioxon-2-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole ( 42 ).

Step 5 : Preparation of 3- chloro- 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2,3-b] Pyridin- 3 -yl )-5-( trifluoromethoxy ) benzoic acid P-0355 : To 3,5-dimethyl-4-(1-(tetrahydro-2H-piper Pyran-4-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)-1H-pyrrolo[2,3-b] Pyridin-5-yl)isoxazole ( 42 , 0.1 g, 0.24 mmol), methyl 4-bromo-3-chloro-5-(trifluoromethoxy)benzoate ( 40 , 0.12 g, 0.35 mmol) and Add 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (20 mg, 0.025 mmol) to the mixture of dioxane (3 ml) Aqueous 1 M potassium carbonate (0.47 ml). The reaction was stirred at 100°C for 3 hours. The reaction was allowed to cool and then diluted with ethyl acetate and evaporated onto silica. The methyl ester intermediate was purified by silica gel column chromatography (0-100% ethyl acetate/hexane). The resulting methyl ester of P-0355 was dissolved in methanol/THF (1:1, 4 ml) and aqueous 1 M lithium hydroxide (1.18 ml) was added. The mixture was stirred at room temperature for 3 hours. The reaction was quenched with sodium sulfate extracted with solids, filtered and the filtrate was concentrated under reduced pressure. By reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) Purify the material to obtain 3-chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)- 1H-pyrrolo[2,3-b]pyridin-3-yl)-5-(trifluoromethoxy)benzoic acid ( P-0355 ). MS (ESI) [M+H ⁺ ] ⁺ = 536.0. Example 10

Step 1 : Preparation of 1- oxidized 5- bromo -2-( methoxycarbonyl )-4 -methylpyridine 44 : to contain methyl 5-bromo-4-methylpicolinate ( 43 , 1.00 g, 4.35 mmol) Add mCPBA (77%, 3.00 g, 13.39 mmol) to 1,2-dichloroethane (10 ml) all at once. The reaction mixture was stirred at room temperature for 16 hours. The reaction was filtered and the filtrate was concentrated under reduced pressure. The material was purified by silica gel column chromatography (0-100% ethyl acetate/hexane). This produces 1-oxy 5-bromo-2-(methoxycarbonyl)-4-methylpyridine ( 44 ). MS (ESI) [M+H ⁺ ] ⁺ = 246.0.

Step 2 : Preparation of methyl 5- bromo -6- hydroxy- 4 -methylpicolinate 45 : To 1-oxy 5-bromo-2-(methoxycarbonyl)-4 under argon and cooled to 0°C -To a solution of picoline ( 44 , 480 mg, 1.95 mmol) in dichloromethane (5 mL) and triethylamine (0.8 ml, 5.74 mmol) was added trifluoroacetic anhydride (0.7 ml, 5.04 mmol). The reaction mixture was allowed to warm to room temperature and then quenched by adding water (5 ml). The reaction mixture was extracted with ethyl acetate and water. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (0-75% ethyl acetate/hexane). This produces methyl 5-bromo-6-hydroxy-4-methylpicolinate ( 45 ). MS (ESI) [M+H ⁺ ] ⁺ = 246.0.

Step 3 : Preparation of methyl 5- bromo -6- ethoxy- 4 -methylpicolinate 46 : Methyl 5-bromo-6-hydroxy-4-methylpicolinate ( 45 , 50 mg, 0.2 mmol) A mixture of cesium carbonate (150 mg, 0.46 mmol) in N,N-dimethylformamide (2 ml) was heated to 90°C for 10 minutes. Next, ethyl iodide (0.5 ml, 5.18 mmol) was added and the reaction was stirred at 90°C for 4 hours. The reaction mixture was diluted with THF (20 ml) and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (0-70% ethyl acetate/hexane). This produces methyl 5-bromo-6-ethoxy-4-picolinate ( 46 ). MS (ESI) [M+H ⁺ ] ⁺ = 274.0 and 276.0.

Step 4 : Preparation of 4-(1-( dicyclopropylmethyl )-3- iodo- 1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxan Azole 47 : At 0 ℃, to 4-(3-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 3 , 18 g , 53.1 mmol, 1 equivalent), compound 10 (8.93 g, 80 mmol, 1.5 equivalents) and triphenylphosphine (34.8 g, 133 mmol, 2.5 equivalents) in THF (185 ml) were added dropwise to a solution of azo Diisopropyl dicarboxylate (26.1 ml, 133 mmol, 2.5 equivalents). The reaction was warmed to room temperature and stirred overnight. The reaction was poured into saturated sodium bicarbonate (500 ml) and extracted with ethyl acetate (300 ml). The organic layer was washed with saturated brine (500 ml) and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (0-50% ethyl acetate/heptane). The product was wet-milled with an approximately 1:1 mixture of MTBE and heptane (approximately 50 ml) to obtain 4-(1-(dicyclopropylmethyl)-3-iodo-1H-pyrrolo[2,3-b ]Pyridin-5-yl)-3,5-dimethylisoxazole ( 47 ).

Step 5 : Preparation of 4-(1-( dicyclopropylmethyl )-3-(4,4,5,5 -tetramethyl -1,3,2- dioxaboron -2- yl )- 1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxazole 48 : at 0℃, to 4-(1-(dicyclopropylmethyl)- 3-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 47 , 4 g, 9.23 mmol, 1 equivalent) in THF (90 ml Add 2 M isopropyl magnesium chloride (11.1 ml, 22.16 mmol, 2.4 equivalents) in THF to the solution in ). After stirring for 30 minutes, the completion of metal/halogen exchange was determined by 1H NMR. Isopropyltetramethylethylene glycol borate (11.3 ml, 55.4 mmol, 6 equivalents) was added and the reaction was allowed to warm to room temperature and stirred overnight. The reaction was poured into water (200 ml) and adjusted to pH 6 with 10% aqueous acetic acid (about 40 ml). The mixture was extracted with ethyl acetate (200 ml). The organic layer was washed with saturated brine (200 ml) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-100% ethyl acetate/heptane) to obtain 4-(1-(dicyclopropylmethyl)-3-(4,4,5,5-tetra Methyl-1,3,2-dioxoboron-2-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 48 ).

Step 6: Preparation of 5- (1- (dicyclopropylmethyl) -5- (3,5-dimethyl-4-yl) lH-pyrrolo [2,3-b] pyridin - 3- yl )-6- ethoxy- 4 -picolinate methyl ester 49 : to contain 4-(1-(dicyclopropylmethyl)-3-(4,4,5,5-tetramethyl) Base-1,3,2-dioxoboron-2-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 48 , 55 mg, 0.127 mmol), 5-bromo-6-ethoxy-4-methylpicolinate ( 46 , 17 mg, 0 mol) and 1,1'-bis(diphenylphosphino) dicene Iron-palladium(II) dichloride dichloromethane complex (14 mg, 0.017 mmol) in 1,4-dioxane (2 ml) was added with aqueous 1 M potassium carbonate (1 ml). The reaction mixture was stirred at 90°C for 15 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed successively with water and brine, and then dried over anhydrous magnesium sulfate. Remove volatiles under reduced pressure. The material was purified by silica gel column chromatography (0-75% ethyl acetate/hexane). This produces 5-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-6-ethoxy-4-methylpicolinate ( 49 ). MS (ESI) [M+H ⁺ ] ⁺ = 501.2.

Step 7: Preparation of 5- (1- (dicyclopropylmethyl) -5- (3,5-dimethyl-4-yl) lH-pyrrolo [2,3-b] pyridin - 3- yl )-6- ethoxy- 4 -methylpicolinic acid P-0417 : To contain 5-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazole) -4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-ethoxy-4-methylpicolinate ( 49 , 27 mg, 0.05 mmol) in THF ( 10 ml) add 1 M lithium hydroxide (5 ml) in water. The reaction mixture was stirred at room temperature for 5 hours. After the addition of aqueous formic acid, the organic layer of the reaction mixture was separated and concentrated under reduced pressure. By reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) Purify the material to obtain 5-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b] Pyridin-3-yl)-6-ethoxy-4-methylpicolinic acid ( P-0417 ). MS (ESI) [M+H ⁺ ] ⁺ = 487.2. Example 11

Step 1 : Preparation of 4-(3- iodo- 1 -tosyl- 1H- pyrrolo [3,2-b] pyridin -6- yl )-3,5 -dimethylisoxazole 50 : To Containing 4-(3-iodo-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxazole ( 8 , 1.2 g, 3.54 mmol) in THF (50 ml) was added sodium hydride (60%, 0.17 mg, 4.25 mmol). The mixture was stirred at room temperature for 30 minutes. Next, 4-methylbenzenesulfonyl chloride (1.01 g, 5.31 mmol) was added and the reaction was stirred for 3 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed successively with water and brine, then dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The material was purified by silica gel column chromatography (0-45% ethyl acetate/hexane). This produces 4-(3-iodo-1-tosyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxazole ( 50 ). MS (ESI) [M+H ⁺ ] ⁺ = 494.1.

Step 2 : Preparation of bicyclopropyl (6-(3,5 -dimethylisoxazol- 4 -yl )-1 -toluenesulfonyl- 1H- pyrrolo [3,2-b] pyridine- 3- Base ) methanol 51 : to 4-(3-iodo-1-toluenesulfonyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-bis cooled to -55°C To a solution of methylisoxazole ( 50 , 866 mg, 1.76 mmol) in THF (5 ml) was added 2 M isopropylmagnesium chloride in THF (1.5 ml). The reaction mixture was slowly warmed to 0°C for about 1 hour. The reaction mixture was cooled to -55°C, and then dicyclopropyl ketone (0.35 ml, 3.05 mmol) was added. The reaction mixture was slowly warmed to room temperature over 1-2 hours and kept at room temperature for 90 minutes. The reaction was quenched with aqueous 1 N HCl (3 ml). The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed successively with water and brine, then dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The material was purified by silica gel column chromatography (0-80% ethyl acetate/hexane). This produces bicyclopropyl (6-(3,5-dimethylisoxazol-4-yl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl) Methanol ( 51 ). MS (ESI) [M+H ⁺ ] ⁺ = 478.1.

Step 3 : Preparation of bicyclopropyl (6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b] pyridin- 3 -yl ) methanol 52 : to two Cyclopropyl(6-(3,5-dimethylisoxazol-4-yl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)methanol ( 51 , 390 mg, 0.817 mmol) was added 1 M potassium hydroxide in methanol (10 ml). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed successively with water and brine, then dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain dicyclopropyl(6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl)methanol ( 52 ).

Step 4 : Preparation of 4-(3-( dicyclopropyl ( hydroxy ) methyl )-6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b ] Pyridin- 1 -yl )-3,5 -diethoxybenzoic acid ethyl ester 53 : to dicyclopropyl(6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrole And [3,2-b]pyridin-3-yl)methanol ( 52 , 100 mg, 0.309 mmol), tripotassium phosphate (140 mg, 0.660 mmol), copper(I) iodide (13 mg, 0.068 mmol), Trans N,N'-dimethylcyclohexane-1,2-diamine (100 mg, 0.703 mmol) and 4-bromo-3,5-diethoxy-ethyl benzoate (160 mg, 0.504 mmol) ) Add toluene (2 ml). The reaction mixture was heated to 110°C for 16 hours. The reaction mixture was filtered and the filtrate was concentrated to dryness under reduced pressure. The material was purified by silica gel column chromatography (0-8% methanol/dichloromethane). This produces 4-(3-(dicyclopropyl(hydroxy)methyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine -1-yl)-3,5-diethoxy ethyl benzoate ( 53 ). MS (ESI) [M+H ⁺ ] ⁺ = 560.6.

Step 5 : Preparation of 4-(3-( dicyclopropyl ( hydroxy ) methyl )-6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b ] Pyridin- 1 -yl )-3,5 -diethoxybenzoic acid P-0165 : To contain 4-(3-(dicyclopropyl(hydroxy)methyl)-6-(3,5-dimethyl Isoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid ethyl ester ( 53 , 17 mg, 0.030 mmol) Add aqueous 1 M lithium hydroxide (5 ml) to THF (10 ml). The reaction mixture was stirred at room temperature for 20 hours. The organic layer of the reaction mixture was collected and concentrated under reduced pressure. By reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) Purify the material to obtain 4-(3-(dicyclopropyl(hydroxy)methyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3 ,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid ( P-0165 ). MS (ESI) [M+H ⁺ ] ⁺ = 532.15. Example 12

Step 1 : Preparation of (6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2-b] pyridin- 3 -yl )( pyridin -2- yl ) methanol 54 : Stir 3,5-dimethyl-4-(1H-pyrrolo[3,2-b]pyridin-6-yl)isoxazole ( 11 , 213 mg, 1.00 mmol), pyridine-2 at room temperature -A mixture of formaldehyde (161 mg, 1.50 mmol) and potassium hydroxide (281 mg, 5.00 mmol) in methanol (10 ml) for 15 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and by reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5 % H ₂ O, 0.1% HCO ₂ H) to obtain (6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl ) (Pyridin-2-yl)methanol ( 54 ). MS (ESI) [M+H ⁺ ] ⁺ = 321.1.

Step 2 : Preparation of 3,5 -dimethyl- 4-(3-( pyridin -2 -ylmethyl )-1H- pyrrolo [3,2-b] pyridin -6- yl ) isoxazole 55 : (6-(3,5-Dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl)(pyridin-2-yl)methanol ( 54 , 210 mg , 0.656 mmol) Triethylsilane (0.52 ml, 3.28 mmol) and trifluoroacetic acid (0.25 ml, 3.28 mmol) were added to a mixture of dichloroethane (6 ml). The mixture was stirred at 80°C for 2 hours. The reaction was quenched with saturated aqueous potassium carbonate solution and extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain 3,5-dimethyl-4-(3-(pyridin-2-ylmethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)isoxan Azole ( 55 ). MS (ESI) [M+H ⁺ ] ⁺ = 305.1.

Step 3 : Preparation of 4-(6-(3,5 -dimethylisoxazol- 4 -yl )-3-( pyridin -2 -ylmethyl )-1H- pyrrolo [3,2-b] pyridine -1 -yl )-3-( trifluoromethoxy ) benzoic acid P-0159 : To contain 3,5-dimethyl-4-(3-(pyridin-2-ylmethyl)-1H-pyrrolo [3,2-b]Pyridin-6-yl)isoxazole ( 55 , 33 mg, 0.108 mmol) and copper(I) bromide (10 mg, 0.070 mmol) of N,N-dimethylformamide (2 ml) was added methyl 4-bromo-3-(trifluoromethoxy)benzoate (50 mg, 0.167 mmol) and potassium carbonate (50 mg, 0.362 mmol). The mixture was heated to 100°C for 10 minutes. Next, sodium hydroxide (100 mg, 2.50 mmol) and copper (II) acetate monohydrate (10 mg, 0.050 mmol) were added to the reaction mixture. The reaction mixture was heated to 110°C for 6 days. The reaction was cooled to room temperature and filtered. The filtrate was concentrated to dryness under reduced pressure. The resulting residue was extracted with water (+1 N citric acid) and ethyl acetate.

The organic layer was washed successively with water and brine, then dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and by reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5 % H ₂ O, 0.1% HCO ₂ H) to obtain 4-(6-(3,5-dimethylisoxazol-4-yl)-3-(pyridin-2-ylmethyl)-1H -Pyrrolo[3,2-b]pyridin-1-yl)-3-(trifluoromethoxy)benzoic acid ( P-0159 ). MS (ESI) [M+H ⁺ ] ⁺ = 509.5. Example 13

Step 1 : Preparation of ethyl 4- bromo -3,5 -diethoxy -2- fluorobenzoate 57 : To the ethyl 4-bromo-3,5-diethoxybenzoate ( 56 , 1.02 g, 3.20 mmol) of acetonitrile (20 ml) was added ditetrafluoroborate 1-(chloromethyl)-4-fluoro-1,4-diazenium bicyclo[2.2.2]octane (2.08 g, 5.87 mmol). The reaction mixture was immediately heated at 60°C. After 18 hours, the reaction mixture was diluted with ethyl acetate and extracted with water (+HCl). The organic layer was washed successively with saturated aqueous sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (0 to 20% ethyl acetate/DCM 40/60 in hexane). Combine the eluted fractions of the previous operation mix and purify with the second column. The eluted fractions mixed in the reverse operation are combined and purified with a third column. This produces the mono-F product, ethyl 4-bromo-3,5-diethoxy-2-fluorobenzoate ( 57 ). MS (ESI) [M+H ⁺ ] ⁺ = 334.9.

Step 2 : Preparation of 4-(1-(2,4 -difluorophenyl )-1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxazole 58 : Add 3,5-dimethyl-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole ( 3a , 1.91 g, 8.97 mmol) to a pressure vessel with a magnetic stirring bar , 1-bromo-2,4-difluoro-benzene (4.71 g, 24.4 mmol), copper(I) iodide (521 mg, 2.74 mmol), potassium hydroxide (0.884 g, 15.8 mmol) and 1,4- Dioxane (50 ml). Then, (1R,2R)-N1,N2-dimethylcyclohexane-1,2-diamine (0.524 g, 3.68 mmol) was added and the reactant was purged with argon, sealed and kept at 120° C. Stir in an oil bath. After 17 hours, the reaction was filtered through Celite and washed with ethyl acetate. The filtrate was extracted with 1 M HCl aqueous solution (2 times) and brine (1 time). The organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated and eluted with a gradient of 20 to 50% ethyl acetate/hexane. The resulting residue was purified by silica gel flash column chromatography to obtain 4-(1-(2,4 -Difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 58 ). MS (ESI) [M+H ⁺ ] ⁺ = 326.4.

Step 3 : Preparation of 4-(1-(2,4 -difluorophenyl )-3- iodo- 1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethyl Isoxazole 59 : To 4-(1-(2,4-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole (58, 825 mg, 2.54 mmol ) in acetonitrile was added succinic iodine N- (PEI) (857 mg, 3.81 mmol) ( 20 ml) in the solution. The reaction was stirred at room temperature for 22 hours. TLC indicates that all starting material has been consumed. The reaction was poured into ethyl acetate and saturated aqueous sodium thiosulfate solution and the layers were separated. The organic layer was washed with saturated aqueous sodium thiosulfate solution and then with brine, dried over anhydrous magnesium sulfate and filtered. The volatiles were removed by rotary evaporation and eluted with 0-20% ethyl acetate/hexane, and the resulting residue was purified by silica gel flash column chromatography. This produces 4-(1-(2,4-difluorophenyl)-3-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxan Azole ( 59 ). MS (ESI) [M+H ⁺ ] ⁺ = 451.9.

Step 4 : Preparation of 4-(1-(2,4 -difluorophenyl )-3-(4,4,5,5 -tetramethyl -1,3,2- dioxaboron -2- yl )-1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxazole 60 : To be equipped with 4-(1-(2,4-difluorophenyl) -3-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 59 , 956 mg, 2.12 mmol), Pd X-Phos G1 ( Add 1,4-dioxane (16 ml) to a round bottom flask with 152 mg, 0.206 mmol) and pinacol borane (1.23 ml, 8.48 mmol). The stirred solution was purged with argon and then triethylamine (1.48 ml, 10.6 mmol) was added, and the reactants were placed in an oil bath at 60° C. under an argon atmosphere for 1.5 hours. TLC indicated that the starting iodide was exhausted. The cooled reaction was diluted with ethyl acetate (25 ml) and brine (25 ml), stirred for 30 minutes and filtered through Celite, washing with ethyl acetate. The layers were separated and the organic layer was dried over anhydrous sodium sulfate and filtered. The volatiles were removed by rotary evaporation and eluted with 0-20% ethyl acetate/hexane. The resulting residue was purified by silica gel flash column chromatography to obtain 4-(1-(2,4-difluorophenyl) )-3-(4,4,5,5-Tetramethyl-1,3,2-dioxoboron-2-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl )-3,5-Dimethylisoxazole ( 60 ). MS (ESI) [M+H ⁺ ] ⁺ = 452.0.

Step 5 : Preparation of 4-(1-(2,4 -difluorophenyl )-5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3-b] (Pyridin- 3 -yl )-3,5 -diethoxy -2- fluorobenzoic acid ethyl ester 61 : Add 4-(1-(2,4-difluorophenyl) to a pressure vessel with a magnetic stir bar -3-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl) -3,5-Dimethylisoxazole ( 60 , 662 mg, 1.47 mmol), 4-bromo-3,5-diethoxy-2-fluoro-benzoic acid ethyl ester ( 57 , 485 mg, 1.45 mmol) ), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (239 mg, 0.293 mmol) and 1,4-dioxane (7 ml ). Then, 2.5 M potassium carbonate-containing water (2.32 ml) was added and the reaction was purged with argon, sealed and immediately heated in an oil bath at 120° C. for 15 minutes. The reaction mixture was allowed to cool and poured into water (20 ml) and ethyl acetate (20 ml) and filtered through celite. The organic layer was washed with 1 M HCl aqueous solution to produce a black, solid material, which was removed by filtration through celite. The organic layer was washed with brine, then dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and eluted with a gradient of 20-50% ethyl acetate/hexane, and purified by silica gel column chromatography to obtain 4-(1-(2,4-difluorophenyl)-5- (3,5-Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3,5-diethoxy-2-fluorobenzoic acid ethyl Esters ( 61 ). MS (ESI) [M+H ⁺ ] ⁺ = 580.4.

Step 6 : Preparation of 4-(1-(2,4 -difluorophenyl )-5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3-b] Pyridin- 3 -yl )-3,5 -diethoxy -2- fluorobenzoic acid P-0297 : To 4-(1-(2,4-difluorophenyl) dissolved in THF (8.7 ml) -5-(3,5-Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3,5-diethoxy-2-fluoro To ethyl benzoate ( 61 , 142 mg, 0.25 mmol) was added aqueous 1 M lithium hydroxide (4.6 ml) and the two-phase mixture was stirred at room temperature for 5 hours. The reaction was quenched with aqueous 2 N HCl (3 ml) and diluted with ethyl acetate (20 ml). The organic layer was washed with brine and then dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the material was purified by silica gel flash column chromatography (0 to 10% methanol/dichloromethane) to give 4-(1-(2,4-difluorophenyl)-5-( 3,5-Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3,5-diethoxy-2-fluorobenzoic acid ( P -0297 ). MS (ESI) [M+H ⁺ ] ⁺ = 552.1. Example 14

Step 1 : Preparation of 4-(6 -chloropyridin- 3 -yl )-3,5 -dimethylisoxazole 64 : Add to 5-bromo-2-chloro-pyridine ( 63 , 2.00 g, 10.4 mmol) 3,5-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)isoxazole ( 62 , 2.55 g, 11.4 mol ), aqueous 1 M potassium carbonate (15.59 ml), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (0.76 g, 0.93 mmol) and Dioxane (10 ml). The reaction was heated to 60°C for 2 hours. The reaction was poured into brine and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and then evaporated onto silica. The product was separated by silica gel flash column chromatography (0 to 100% ethyl acetate/hexane) to obtain 4-(6-chloropyridin-3-yl)-3,5-dimethylisoxazole ( 64 ) . MS (ESI) [M+H ⁺ ] ⁺ = 209.1.

Step 2 : Preparation of 5-(3,5 -dimethylisoxazol- 4 -yl )-N-(3 -methyltetrahydrofuran- 3 -yl ) pyridin -2- amine 65 : In a 20 mL microwave vial, Dissolve 4-(6-chloropyridin-3-yl)-3,5-dimethylisoxazole ( 64 , 0.5 g, 2.4 mmol) in DME (2 ml). Next, add 3-methyloxolane-3-amine (0.3 ml, 2.88 mmol), sodium tert-butoxide (345 mg, 3.59 mmol) and RuPhos (196 mg, 0.24 mmol) and seal the vial and place it in a nitrogen atmosphere Bottom, heated to 120°C in an oil bath for 18 hours. The reaction mixture was filtered through celite and then evaporated onto silica. By reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% The _{substance was purified by HCO 2} H) to obtain 5-(3,5-dimethylisoxazol-4-yl)-N-(3-methyltetrahydrofuran-3-yl)pyridin-2-amine ( 65 ). MS (ESI) [M+H ⁺ ] ⁺ = 274.2.

Step 3 : Preparation of 5-(3,5 -dimethylisoxazol- 4 -yl )-3- iodo- N-(3 -methyltetrahydrofuran- 3 -yl ) pyridin -2- amine 66 : at 20 ml microwave vial, make 5-(3,5-dimethylisoxazol-4-yl)-N-(3-methyltetrahydrofuran-3-yl)pyridin-2-amine ( 65 , 515 mg, 1.88 mmol) was dissolved in DMF (8 ml). Add trifluoroacetic acid (0.42 ml, 5.65 mmol) and N-iodosuccinimide (636 mg, 2.83 mmol) and seal the vial and heat to 80°C for 4 hours. The reaction mixture was poured on sodium thiosulfate, filtered and then evaporated onto silica gel. The product was separated by silica gel flash column chromatography (0 to 100% ethyl acetate/hexane) to obtain 5-(3,5-dimethylisoxazol-4-yl)-3-iodo-N- (3-Methyltetrahydrofuran-3-yl)pyridin-2-amine ( 66 ). MS (ESI) [M+H ⁺ ] ⁺ = 399.9.

Step 4 : Preparation of 3,5 -dimethyl- 4-(1-(3 -methyltetrahydrofuran- 3 -yl )-1H- pyrrolo [2,3-b] pyridin -5- yl ) isoxazole 67 : In a 5 ml microwave vial, make 5-(3,5-dimethylisoxazol-4-yl)-3-iodo-N-(3-methyltetrahydrofuran-3-yl)pyridine-2- Amine ( 66 , 0.5 g, 1.25 mmol) and (E)-1-ethoxyethylene-2-boronic acid pinacol ester (0.413 ml, 1.88 mmol) were dissolved in DMF (3 ml). Then, 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (92 mg, 0.11 mmol) and lithium hydroxide (90 mg, 3.76 mmol) were added ) The vial is sealed and heated to 80°C in an oil bath for 6 hours under a nitrogen atmosphere. Then, the reaction was cooled to 50°C and 25% aqueous HCl (0.37 ml, 2.5 mmol) was added via a syringe and the reaction was stirred for 2 hours. The reaction was poured into saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was evaporated onto silica gel and purified by silica gel flash column chromatography (0 to 10% methanol/dichloromethane) to obtain 3,5-dimethyl-4-(1-(3-methyltetrahydrofuran- 3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole ( 67 ). MS (ESI) [M+H ⁺ ] ⁺ = 298.1.

Step 5 : Preparation of 4-(3- iodo- 1-(3 -methyltetrahydrofuran- 3 -yl )-1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5- dimethyl Isoxazole 68 : Make 3,5-dimethyl-4-(1-(3-methyltetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl) Oxazole ( 67 , 340 mg, 1.14 mmol) was dissolved in DMF (3 ml) and cooled to 0°C. Next, add a solution of N-iodosuccinimide (309 mg, 1.37 mmol) in DMF (2 mL). The reaction was stirred for 2 hours while warming to room temperature. The reaction was poured into saturated aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was evaporated onto silica and purified by silica gel flash column chromatography (0 to 100% ethyl acetate/hexane) to give 4-(3-iodo-1-(3-methyltetrahydrofuran-) 3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 68 ).

Step 6 : Preparation of 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1-(3 -methyltetrahydrofuran- 3 -yl )-1H- pyrrolo [2,3-b ] Pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid P-0383 : make 4-(3-iodo-1-(3-methyltetrahydrofuran-3-yl)-1H-pyrrolo [2,3-b]pyridin-5-yl)-3,5-dimethylisoxazole ( 68 , 50 mg, 0.12 mmol) and 4-(4,4,5,5-tetramethyl-1 ,3,2-Dioxon-2-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 25 , 61 mg, 0.18 mmol) was dissolved in dioxane (3 ml), and then Add aqueous 1 M potassium carbonate (0.24 ml) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (9 mg, 0.01 mmol). The reaction was stirred at 110°C for 4 hours. The reaction was diluted with ethyl acetate and evaporated onto silica gel. The methyl ester intermediate was separated by silica gel flash column chromatography (0 to 100% ethyl acetate/hexane). The separated product was dissolved in MeOH/THF (4 ml) and aqueous 1 M lithium hydroxide (0.59 ml) and stirred at room temperature for 4 hours. The reactant was poured into saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was evaporated onto the silica gel and subjected to reverse phase silica gel flash column chromatography (0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) to obtain 4-(5-(3,5-dimethylisoxazol-4-yl)-1-(3-methyltetrahydrofuran-3) -Yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid ( P-0383 ). MS (ESI) [M+H ⁺ ] ⁺ = 502.0. Example 15

Step 1 : Preparation of 3,5 -dimethyl- 4-(2- methyl -1H- pyrrolo [2,3-b] pyridin -5- yl ) isoxazole 70 : To the 5- Bromo-2-methyl-1H-pyrrolo[2,3-b]pyridine ( 69 , 2.01 g, 9.5 mmol), 3,5-dimethyl-4-(4,4,5,5-tetramethyl -1,3,2-dioxoboron-2-yl)isoxazole (4.24 g, 19 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium dichloride (II) A mixture of dichloromethane complex (695 mg, 0.852 mmol) in dioxane (60 ml) was added with aqueous 2.5 M potassium carbonate (12 ml). The mixture was heated at 110°C for 3 hours. The reaction was cooled and diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel flash column chromatography (40% ethyl acetate/hexane) to obtain 3,5-dimethyl-4-(2-methyl-1H-pyrrolo[2 ,3-b]pyridin-5-yl)isoxazole ( 70 ). MS (ESI) [M+H ⁺ ] ⁺ = 228.1.

Step 2 : Preparation of 4-(3- iodo- 2- methyl -1H- pyrrolo [2,3-b] pyridin -5- yl )-3,5 -dimethylisoxazole 71 : towards ice-cold 3,5-Dimethyl-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole ( 70 , 1.00 g, 4.4 mmol) in acetonitrile (40 ml Add N-iodosuccinimide (1.09 g, 4.84 mmol) to the solution in ). The mixture was stirred at 0°C for 2 hours. The reaction was diluted with saturated aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the material was purified by silica gel flash column chromatography (50% ethyl acetate/hexane) to give 4-(3-iodo-2-methyl-1H-pyrrolo[2,3 -b]pyridin-5-yl)-3,5-dimethylisoxazole ( 71 ). MS (ESI) [M+H ⁺ ] ⁺ = 354.0.

Step 3 : Preparation of 2-(5-(3,5 -dimethylisoxazol- 4 -yl )-3- iodo- 2- methyl -1H- pyrrolo [2,3-b] pyridine -1 - yl) nicotinic nitrile 72: A solution of 4- (3-iodo-2-methyl -1H- pyrrolo [2,3-b] pyridin-5-yl) -3,5-dimethyl deg.] C at 100 Mixture of ylisoxazole ( 71 , 353 mg, 1.00 mmol), potassium carbonate (276 mg, 2.00 mmol) and 2-fluoropyridine-3-carbonitrile (244 mg, 2.00 mmol) in DMF (5 ml) 3 hour. The reaction was cooled and diluted with water and extracted with ethyl acetate. The filtrate was washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel flash column chromatography (70% ethyl acetate/hexane) to obtain 2-(5-(3,5-dimethylisoxazol-4-yl)- 3-Iodo-2-methyl-1H-pyrrolo[2,3-b]pyridin-1-yl)nicotinonitrile ( 72 ). MS (ESI) [M+H ⁺ ] ⁺ = 456.0.

Step 4 : Preparation of 4-(1-(3- cyanopyridin -2- yl )-5-(3,5 -dimethylisoxazol- 4 -yl )-2- methyl -1H- pyrrolo [ 2,3-b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid methyl ester 73 : to 2-(5-(3,5-dimethylisoxazole) purged with nitrogen -4-yl)-3-iodo-2-methyl-1H-pyrrolo[2,3-b]pyridin-1-yl)nicotinonitrile ( 72 , 100 mg, 0.22 mmol), 4-(4 ,4,5,5-Tetramethyl-1,3,2-dioxoboron-2-yl)-3-(trifluoromethoxy)methyl benzoate ( 25 , 99 mg, 0.29 mmol) And 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (18 mg, 0.022 mmol) in a mixture of dioxane (2 ml) Add 2.5 M aqueous potassium carbonate (0.270 ml). The reaction was heated at 110°C for 3 hours. The reaction was cooled to room temperature and diluted with ethyl acetate, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel flash column chromatography (70% ethyl acetate/hexane) to obtain 4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethyl Isoxazol-4-yl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 73 ). MS (ESI) [M+H ⁺ ] ⁺ = 548.2.

Step 5 : Preparation of 4-(1-(3- cyanopyridin -2- yl )-5-(3,5 -dimethylisoxazol- 4 -yl )-2- methyl -1H- pyrrolo [ 2,3-b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid P-0345 : To 4-(1-(3-cyanopyridin-2-yl)-5-(3 ,5-Dimethylisoxazol-4-yl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid To a mixture of ester (73 , 116 mg, 0.21 mmol) in (1:1) THF/MeOH (2.0 ml) was added aqueous 4.18 M lithium hydroxide (0.150 ml). The mixture was stirred at 70°C for 2 hours. The reaction was diluted with ethyl acetate, acidified with 1 N HCl in MeOH and concentrated under reduced pressure. By reverse phase silica gel flash column chromatography (0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O , 0.1% HCO ₂ H) to purify the material to obtain 4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-2-methan Group-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid ( P-0345 ). MS (ESI) [M+H ⁺ ] ⁺ = 534.0. Example 16

Step 1 : Preparation of (3 -methylisoxazole- 5- yl ) methanol 75 : Add 3-methylisoxazole-5-carboxylic acid ( 74 , 6.36 g, 50 mmol) to 3-methylisoxazole-5-carboxylic acid (74, 6.36 g, 50 mmol) at 0°C over 5 minutes To a solution of TEA (8.36 mL, 60 mmol) in THF (150 mL) was added isobutyl chloroformate (7.13 mL, 55 mmol). Then, the mixture was stirred at 0°C for 5 minutes and at room temperature for 10 minutes. The precipitate was removed by filtration and the precipitate was washed with THF (50 mL), then the mother liquor and the washed solution were combined and cooled to 0°C. At 0°C, water (5 ml) was added to the solution and then sodium borohydride (3.78 g, 100 mmol) was slowly added to the solution at 0°C over 15 minutes. Then, also carefully add water (35 mL). The resulting mixture was stirred at 0°C for 1 hour, and then stirred at room temperature for 30 minutes. After the reaction mixture was cooled to 0°C, to the solution was slowly added aqueous 4 N sulfuric acid (80 mL) and the mixture was extracted with ethyl acetate (400 mL). The extract was washed with water (50 mL and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. This produced (3-methylisoxazol-5-yl)methanol ( 75 ).

Step 2 : Preparation of 3 -methylisoxazole- 5- carbaldehyde 76 : To (3-methylisoxazole-5-yl)methanol ( 75 , 3.50 g, 27 mmol) in dichloromethane at 0°C To the solution in (140 mL) was added Dess-Martin periodinane (13.9 g, 32.7 mmol) and the mixture was stirred at room temperature for 6.5 hours. The mixture was diluted with dichloromethane (500 mL) and washed with aqueous 5% sodium thiosulfate (150 mL) and aqueous saturated sodium bicarbonate (150 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (0-40% ethyl acetate/hexane) to obtain 3-methylisoxazole-5-carbaldehyde ( 76 ).

Step 3 : Preparation of 3- methyl -5 -vinylisoxazole 77 : Add 3-methylisoxazole-5-carbaldehyde ( 76 , 1.91 g, 17.19 mmol) in THF ( Add ((trimethylsilyl)methyl)magnesium chloride solution (1.0 M in THF, 25.8 mL, 25.8 mmol) to the solution in 25 mL) dropwise. After stirring at 0°C for 1 hour, the solution was warmed to room temperature and stirred for 6.5 hours. At 0°C, aqueous 1 N sulfuric acid (25 mL) was added and the reaction was extracted with ethyl acetate (100 mL). The organic layer was washed with aqueous saturated sodium bicarbonate (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting TMS-CH2 adduct was dissolved in ether (60 mL) and concentrated sulfuric acid (3.41 mL) was added dropwise at 0°C over 5 minutes. Next, the mixture was stirred at room temperature for 2 hours. The mixture was poured into ice-cold aqueous saturated sodium bicarbonate (40 mL) and the resulting mixture was extracted with ether (160 mL). After washing the organic layer with brine (30 mL), the solution was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 3-methyl-5-vinylisoxazole ( 77 ).

Step 4 : Preparation of 5- ethyl- 3 -methylisoxazole 78 : To a solution of crude 3-methyl-5-vinylisoxazole ( 77 , 2.31 g, 17.2 mmol) in MeOH (120 mL) Add 10% Pd/C (50% wet, 730 mg) to it and stir vigorously under hydrogen for 1 hour at room temperature. After removing the catalyst by filtration through Celite, the mixture was concentrated under reduced pressure to obtain 5-ethyl-3-methylisoxazole ( 78 ).

Step 5 : Preparation of 4- bromo -5- ethyl- 3 -methylisoxazole 79 : Add 5-ethyl-3-methylisoxazole ( 78 , 1.63 g, 14.7 mmol) in DMF (30 mL) To the solution in N-bromosuccinimide (3.13 g, 17.6 mmol) was added and the mixture was stirred at room temperature overnight. After adding additional N-bromosuccinimide (522 mg, 2.93 mmol), the mixture was stirred for another 5 hours at room temperature. The reaction mixture was diluted with ethyl acetate and hexane (1/1, 300 mL) and aqueous 5% sodium thiosulfate (90 mL), aqueous 1 N NaOH (60 mL), water (60 mL) and brine (60 mL) mL) Wash. The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (0 to 10% ethyl acetate/hexane) to give 4-bromo-5-ethyl-3-methylisoxazole ( 79 ).

Step 6: Preparation of 5-ethyl-3-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl Mouth) isoxazole 80: At -78°C, to a solution of 4-bromo-5-ethyl-3-methylisoxazole ( 79 , 161 mg, 0.847 mmol) in THF (4.5 mL) was added dropwise n-BuLi solution ( 2.5 M in hexane, 0.54 mL, 1.36 mmol). After stirring the mixture at -78°C for 20 minutes, add 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxoboron (0.31 mL, 1.53 mmol) and Stir for another 2 hours at -78°C. The reaction was quenched with saturated aqueous ammonium chloride (1 mL), diluted with ethyl acetate (50 mL) and washed with water (30 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (0 to 10% ethyl acetate/hexane) to give 5-ethyl-3-methyl-4-(4,4,5,5-tetramethyl- 1,3,2-Dioxon-2-yl)isoxazole ( 80 ).

Step 7 : Preparation of 5- bromo- 3- iodo- 1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2,3-b] pyridine 82 : at 0°C under 5 Minutes to 5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine ( 81 , 3.23 g, 10.0 mmol), tetrahydro-2H-piperan-4-ol (1.02 mg, 10.0 mmol) ) And triphenylphosphine (3.93 g, 15.0 mmol) in THF (50 mL) were added dropwise diisopropyl azodicarboxylate (2.95 mL, 15.0 mmol), and the mixture was stirred at room temperature 2 day. The reaction was concentrated under reduced pressure and the material was purified by silica gel flash column chromatography (0 to 35% ethyl acetate/hexane). Chromatography or suspend the solid product in ethyl acetate/hexane (1/3 ratio), followed by filtration to further purify the impure fraction. This produces 5-bromo-3-iodo-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine ( 82 ).

Step 8 : Preparation of 4-(5- bromo- 1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2,3-b] pyridin- 3 -yl )-3-( trifluoro (Methoxy ) methyl benzoate 83 : Stir 5-bromo-3-iodo-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3- b] Pyridine ( 82 , 330 mg, 0.811 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)-3-(trifluoro Methoxy) benzoic acid methyl ester ( 25 , 281 mg, 0.811 mmol), PdCl ₂ (Ph ₃ P) ₂ (28.5 mg, 0.041 mmol), sodium carbonate (258 mg, 2.432 mmol), 1,4-dioxin A mixture of alkane (6.4 mL) and water (1.6 mL) overnight. The reaction was concentrated under reduced pressure and then partitioned between ethyl acetate (50 mL) and water (10 mL). The organic layer was separated and washed with brine (10 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude material obtained was purified by silica gel flash column chromatography (0 to 30% ethyl acetate/hexane) to obtain 4-(5-bromo-1-(tetrahydro-2H-piperan-4-yl)-1H -Methyl pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoate ( 83 ).

Step 9 : Preparation of 4-(5-(5- ethyl- 3 -methylisoxazol- 4 -yl )-1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2 ,3-b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid methyl ester 84 : Stir 5-ethyl-3-methyl-4-(4,4,5 at 105°C) ,5-Tetramethyl-1,3,2-dioxoboron-2-yl)isoxazole ( 80 , 26 mg, 0.110 mmol), 4-(5-bromo-1-(tetrahydro-2H) -Piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 83 , 55 mg, 0.110 mmol), Pd(OAc) ₂ (1.2 mg, 0.006 mmol), S-Phos (2.3 mg, 0.006 mol) and K ₃ PO ₄ (58 mg, 0.275 mmol) in dioxane (1.0 mL) and water (0.25 mL) The mixture for 15 hours. The reaction is not complete, so add 5-ethyl-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl) isooxan Azole ( 80 , 26 mg, 0.110 mmol), Pd(OAc) ₂ (1.2 mg, 0.006 mmol), S-Phos (2.3 mg, 0.006 mol) and K ₃ PO ₄ (58 mg, 0.275 mmol) at 105°C The mixture was stirred for another 6 hours. The reaction was allowed to cool, filtered through celite and the filtrate was concentrated under reduced pressure. The resulting mixture of compound 84 and P-0401 was dissolved in DMF (0.5 mL) and potassium carbonate (30 mg, 0.220 mmol) and methyl iodide (0.014 mL, 0.220 mmol) were added, and the mixture was stirred at room temperature overnight. The reaction was diluted with ethyl acetate (50 mL) and the solution was washed with aqueous 0.2 N HCl (5 ml), water (2×5 mL) and brine (5 ml), dried over anhydrous sodium sulfate, filtered and under reduced pressure concentrate. This material was purified by silica gel flash column chromatography (0 to 50% ethyl acetate/hexane) to obtain 4-(5-(5-ethyl-3-methylisoxazol-4-yl)-1 -(Tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 84 ). MS (ESI) [M+H ⁺ ] ⁺ = 530.2.

Step 10 : Preparation of 4-(5-(5- ethyl- 3 -methylisoxazol- 4 -yl )-1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2 ,3-b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid P-0401 : To 4-(5-(5) dissolved in THF (0.75 mL) and MeOH (0.25 mL) -Ethyl-3-methylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) Methyl-3-(trifluoromethoxy)benzoate ( 84 , 31 mg) was added with aqueous 2N lithium hydroxide (0.25 mL, 0.500 mmol) and the reaction was stirred at room temperature for 3 hours. The reaction was quenched by adding aqueous 1 N HCl (0.5 mL), and the mixture was concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (0 to 10% methanol/dichloromethane) to obtain 4-(5-(5-ethyl-3-methylisoxazol-4-yl)-1- (Tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid ( P-0401 ). MS (ESI) [M+H ⁺ ] ⁺ = 516.1. Example 17

Step 1 : Preparation of 4-(5-(3- ethyl -5 -methylisoxazol- 4 -yl )-1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2 ,3-b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid methyl ester 85 : Stir 3-ethyl-5-methyl-4-(4,4,5 at 105°C) ,5-Tetramethyl-1,3,2-dioxoboron-2-yl)isoxazole ( 84 , 26 mg, 0.110 mmol, from 5-methylisoxazole-3-carboxylic acid with such Compound 80 described in Example 16 was prepared in 6 steps in a similar manner), 4-(5-bromo-1-tetrahydropiperan-4-yl-pyrrolo[2,3-b]pyridine-3- Methyl)-3-(trifluoromethoxy)benzoate ( 83 , 55 mg, 0.110 mmol), Pd(OAc) ₂ (1.2 mg, 0.006 mmol), S-Phos (2.3 mg, 0.006 mol) and Mix potassium phosphate (58 mg, 0.275 mmol) in dioxane (1.0 mL) and water (0.25 mL) overnight. Then add 3-ethyl-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)isoxazole ( 84,26 mg, 0.110 mmol), Pd(OAc) ₂ (1.2 mg, 0.006 mmol), S-Phos (2.3 mg, 0.006 mol) and potassium phosphate (58 mg, 0.275 mmol) and the reaction was continued at 105°C for another 6 hours . Then, the reaction was cooled and filtered through Celite. The filtrate was concentrated under reduced pressure. The resulting mixture of compound 85 and P-0400 was dissolved in DMF (0.5 mL) and potassium carbonate (30 mg, 0.220 mmol) and methyl iodide (0.014 mL, 0.220 mmol) were added. The reaction was stirred at room temperature overnight. The reaction was diluted with ethyl acetate (50 mL) and the solution was washed with aqueous 0.2 N HCl (5 ml), water (2×5 mL) and brine (5 ml), dried over anhydrous sodium sulfate, filtered and under reduced pressure concentrate. This material was purified by silica gel flash column chromatography (0 to 50% ethyl acetate/hexane) to obtain 4-(5-(3-ethyl-5-methylisoxazol-4-yl)-1 -(Tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 85 ). MS (ESI) [M+H ⁺ ] ⁺ = 530.2.

Step 2 : Preparation of 4-(5-(3- ethyl -5 -methylisoxazol- 4 -yl )-1-( tetrahydro -2H -piperan- 4 -yl )-1H- pyrrolo [2 ,3-b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid P-0400 : To 4-(5-(3) dissolved in THF (0.75 mL) and MeOH (0.25 mL) -Ethyl-5-methylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) Aqueous 2N LiOH (0.25 mL, 0.500 mmol) was added to methyl-3-(trifluoromethoxy)benzoate ( 85, 47 mg) and stirred at room temperature for 2.5 hours. Then, aqueous 1 N HCl (0.5 mL) was added and the mixture was concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (0 to 10% methanol/dichloromethane) to obtain 4-(5-(3-ethyl-5-methylisoxazol-4-yl)-1- (Tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid ( P-0400 ). MS (ESI) [M+H ⁺ ] ⁺ = 516.1. Example 18

Step 1 : Preparation of (S)-5-(1,4 -dimethyl- 1H-1,2,3- triazol -5- yl )-1-(1-( pyridin -2- yl ) ethyl ) -1H- pyrrolo [2,3-b] pyridine 86 : (S)-5-bromo-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2, 3-b] pyridine ( 17 , 199 mg, 0.66 mmol), 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoboron- 2-yl)triazole (177 mg, 0.79 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (48 mg, 0.059 mmol) ) In dioxane (6.0 ml), and then add aqueous 2.5 M potassium carbonate (0.80 ml). The reaction flask was sealed and heated at 140°C for 2 hours. The reaction was diluted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (100% ethyl acetate) to obtain (S)-5-(1,4-dimethyl-1H-1,2,3-triazol-5-yl) -1-(1-(Pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine ( 86 ). MS (ESI) [M+H ⁺ ] ⁺ = 319.9.

Step 2 : Preparation of (S)-3- bromo -5-(1,4 -dimethyl- 1H-1,2,3- triazol -5- yl )-1-(1-( pyridin -2- yl) ) Ethyl )-1H- pyrrolo [2,3-b] pyridine 87 : to (S)-5-(1,4-dimethyl-1H-1,2,3-triazol-5-yl) -1-(1-(Pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine ( 86 , 50 mg, 0.16 mmol) in acetonitrile (2 ml), add N -Bromosuccinimide (29 mg, 0.16 mmol). The mixture was stirred and warmed to room temperature for 2 hours. The reaction was diluted with saturated aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give (S)-3-bromo-5-(1,4-dimethyl-1H-1,2,3-tri Azol-5-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine ( 87 ). MS (ESI) [M+H ⁺ ] ⁺ = 399.0.

Step 3 : Preparation of (S)-3-(5-(1,4 -dimethyl- 1H-1,2,3- triazol -5- yl )-1-(1-( pyridin -2- yl ) Ethyl )-1H- pyrrolo [2,3-b] pyridin- 3 -yl ) benzoic acid methyl ester 88 : Purging (S)-3-bromo-5-(1,4-dimethyl- 1H-1,2,3-triazol-5-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine ( 87 , 39 mg, 0.10 mmol), methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxoboro-2-yl)benzoate (39 mg, 0.15 mmol) and 1,1 A mixture of'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (8 mg, 0.009 mmol) in dioxane (1 ml), and then water is added 2.5 M potassium carbonate (0.120 ml). The reaction flask was sealed and heated at 130°C for 2 days. The reaction was cooled and diluted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. This material was purified by silica gel flash column chromatography (30% ethyl acetate) to obtain (S)-3-(5-(1,4-dimethyl-1H-1,2,3-triazole-5) -Yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoate ( 88 ). MS (ESI) [M+H ⁺ ] ⁺ = 453.2.

Step 4 : Preparation of (S)-3-(5-(1,4 -dimethyl- 1H-1,2,3- triazol -5- yl )-1-(1-( pyridin -2- yl ) Ethyl )-1H- pyrrolo [2,3-b] pyridin- 3 -yl ) benzoic acid P-0449 : To (S)-3-(5-(1,4-dimethyl-1H-1, 2,3-Triazol-5-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl benzoate ( 88 , 20 mg, 0.04 mmol) was added to a solution of THF/MeOH (1:1, 1.0 ml) in aqueous 4.18 M lithium hydroxide (0.020 ml). The reaction was stirred at 70°C for 2 hours. The reactant was acidified with aqueous 1 N HCl, concentrated under reduced pressure and subjected to reverse phase silica gel flash column chromatography (0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) purified material to obtain (S)-3-(5-(1,4-dimethyl-1H-1,2, 3-Triazol-5-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid ( P-0449 ) . MS (ESI) [M+H ⁺ ] ⁺ = 439.1. Example 19

Step 1 : Preparation of 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1 -tosyl- 1H- pyrrolo [2,3-b] pyridin- 3 -yl ) Methyl- 3-( trifluoromethoxy) benzoate 89 : To 4-(3-iodo-1-toluene-1H-pyrrolo[2,3-b]pyridine- purged with nitrogen 5-yl)-3,5-dimethylisoxazole ( 4 , 1.01 g, 2.05 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxazole) East-2-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 25 , 1.06 g, 3.08 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-dichloride To a mixture of palladium(II) dichloromethane complex (167 mg, 0.205 mmol) in dioxane (20 ml) was added aqueous 2.5 M potassium carbonate (2.5 ml). The reaction flask was sealed and heated at 110°C for 3 hours. The reaction was cooled and diluted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered and concentrated. This material was purified by silica gel flash column chromatography (30% ethyl acetate) to obtain 4-(5-(3,5-dimethylisoxazol-4-yl)-1-tosyl-1H -Pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoate ( 89 ). MS (ESI) [M+H ⁺ ] ⁺ = 586.5.

Step 2 : Preparation of 4-(5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3-b] pyridin- 3 -yl )-3-( trifluoromethyl Oxy ) benzoic acid methyl ester 90 : to 4-(5-(3,5-dimethylisoxazol-4-yl)-1-toluenesulfonyl-1H- dissolved in THF (15 ml) Pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy) benzoic acid methyl ester ( 89 , 865.8 mg, 1.48 mmol) was added to the solution containing 1 M tetra-n-fluoride Butylammonium in THF (1.8 ml). The reaction was stirred at 70°C for 15 hours. The reaction was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate solution, water and brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting solid was wet-milled with dichloromethane/hexane to obtain 4-(5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo Methyl [2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoate ( 90 ). MS (ESI) [M+H ⁺ ] ⁺ = 432.5.

Step 3 : Preparation of 4-(1-(1-( cyanomethyl ) cyclobutyl )-5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3 -b] pyridin- 3 -yl )-3-( trifluoromethoxy) benzoic acid methyl ester 91 : Stir 4-(5-(3,5-dimethylisoxazol-4 -yl) at 80°C )-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 90 , 52 mg, 0.12 mmol), DBU (0.06 ml, 0.48 mmol ) And 2-cyclobutylene acetonitrile (45 mg, 0.48 mmol) in acetonitrile (1 ml) for 15 hours. The reaction was concentrated under reduced pressure and purified by silica gel flash column chromatography (50% ethyl acetate) to give 4-(1-(1-(cyanomethyl)cyclobutyl)-5-(3, 5-Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 91 ). MS (ESI) [M+H ⁺ ] ⁺ = 525.1.

Step 4 : Preparation of 4-(1-(1-( cyanomethyl ) cyclobutyl )-5-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [2,3 -b] pyridin- 3 -yl )-3-( trifluoromethoxy ) benzoic acid P-0335 : to 4-(1-(1-(cyanomethyl)cyclobutyl)-5-(3, 5-Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid methyl ester ( 91 , 55 mg , 0.1 mmol) was added aqueous 4.18 M lithium hydroxide (0.050 ml) to a solution of THF/MeOH (1:1, 1 ml). The reaction was stirred at 70°C for 3 hours. The reaction was diluted with ethyl acetate, acidified with 1 N HCl in MeOH and concentrated under reduced pressure. By reverse phase silica gel flash column chromatography (0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O , 0.1% HCO ₂ H) to purify the material to obtain 4-(1-(1-(cyanomethyl)cyclobutyl)-5-(3,5-dimethylisoxazol-4-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid ( P-0335 ). MS (ESI) [M+H ⁺ ] ⁺ = 511.0. Example 20

Step 1 : Preparation of 3-( cyclobutylmethyl )-6-(3,5 -dimethyl- 4H-1,2,4- triazol- 4 -yl )-1H- pyrrolo [3,2-b] Pyridine 93 : 3,5-dimethyl-4H-1,2,4-triazole (0.50 g, 5.2 mmol), 6-bromo-3-(cyclobutylmethyl)-1H-pyrrolo[ 3,2-b]pyridine ( 92 , 1.0 g, 3.8 mmol, composed of 6-bromo-1H-pyrrolo[3,2-b]pyridine and cyclobutanecarbaldehyde to be similar to compound 55 as depicted in Example 12 The method is prepared in 2 steps), trans N,N'-dimethylcyclohexane-1,2-diamine (1.1 mL, 7.0 mmol) and cesium carbonate (2.5 g, 7.67 mmol) in toluene (5 mL) and DMF (5 mL) and stirred at 130°C for 3 days. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was collected, washed with brine and dried over sodium sulfate. After removing the desiccant and solvent, the residue was purified by silica gel flash column chromatography to obtain 3-(cyclobutylmethyl)-6-(3,5-dimethyl-4H-1,2,4-tri (Azol-4-yl)-1H-pyrrolo[3,2-b]pyridine ( 93 ). MS (ESI) [M+H ⁺ ] ⁺ = 282.1.

Step 2 : Preparation of 4-(3-( cyclobutylmethyl )-6-(3,5 -dimethyl- 4H-1,2,4- triazol- 4 -yl )-1H- pyrrolo [3,2 -b] pyridin- 1 -yl )-3,5 -diethoxybenzoic acid P-0270 : Purge 3-(cyclobutylmethyl)-6-(3,5-dimethyl-4H-1 with nitrogen) ,2,4-Triazol-4-yl)-1H-pyrrolo[3,2-b]pyridine ( 93 , 200 mg, 0.71 mmol), 4-bromo-3,5-diethoxybenzoic acid methyl Ester (300 mg, 0.99 mmol), copper(I) iodide (30 mg, 1.58 mmol) and trans-N,N'-dimethylcyclohexane-1,2-diamine (300 μl, 1.9 mmol) in A mixture of toluene (5 mL) and DMF (5 ml) was stirred at 120°C overnight. The reaction mixture was filtered and subjected to reverse phase HPLC (C18; 0-100% B; A: 5% CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) purify the filtrate to obtain 4-(3-(cyclobutylmethyl)-6-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)- 1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid ( P-0270 ). MS (ESI) [M+H ⁺ ] ⁺ = 490.1. Example 21

Step 1 : Preparation of 6- bromo- 3-( cyclobutylmethyl )-1H- pyrrolo [3,2-c] pyridine- 1- carboxylic acid tert-butyl ester 95 : Make 6-bromo-3-(cyclobutylmethyl) -1H-pyrrolo[3,2-c]pyridine ( 94 , 300 mg, 1.13 mmol, composed of 6-bromo-1H-pyrrolo[3,2-c]pyridine and cyclobutanecarbaldehyde as in Example 12 The depicted compound 55 was prepared in 2 steps in a similar manner), di-tert-butyl dicarbonate (370 mg, 1.70 mmol), DMAP (14 mg, 0.11 mmol) and trimethylamine (0.79 ml, 5.66 mmol) Dissolve in THF and stir at room temperature for 3 hours. Next, the reactant was partitioned between ethyl acetate and aqueous ammonium chloride solution. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and then loaded onto silica gel. Purify the material by silica gel flash column chromatography (0 to 50% ethyl acetate/hexane) to obtain 6-bromo-3-(cyclobutylmethyl)-1H-pyrrolo[3,2-c]pyridine-1 -Tert-butyl formate ( 95 ).

Step 2 : Preparation of 4-(3-( cyclobutylmethyl )-1H- pyrrolo [3,2-c] pyridin -6- yl )-3,5 -dimethylisoxazole 96 : in acetonitrile and dioxane Combination of 6-bromo-3-(cyclobutylmethyl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester ( 95 , 250 mg, 0.68 mmol), 3,5-bis Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)isoxazole (343 mg, 1.54 mmol), aqueous 2.5 M potassium carbonate (0.55 ml) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (50 mg, 0.061 mmol), then purged with argon and In a microwave reactor, it was irradiated to 125°C for 1 hour. Then, the reaction was filtered through Celite and partitioned between ethyl acetate and aqueous ammonium chloride. The organic layer was dried over magnesium sulfate, filtered, and concentrated. Dissolve this material in DCM (3 ml) and trifluoroacetic acid (0.53 ml, 6.84 mmol). The reaction was stirred for 2 hours and then concentrated under reduced pressure. The resulting material was dissolved in ethyl acetate and washed with aqueous sodium bicarbonate solution. The organic layer was further washed with brine, then dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the material was purified by silica gel flash column chromatography (0 to 5% methanol/DCM) to give 4-(3-(cyclobutylmethyl)-1H-pyrrolo[3,2-c] Pyridin-6-yl)-3,5-dimethylisoxazole ( 96 ).

Step 3 : Preparation of 3,5- dichloro- 4-(3-( cyclobutylmethyl )-6-(3,5 -dimethylisoxazol- 4 -yl )-1H- pyrrolo [3,2- c] Pyridin- 1 -yl ) benzoic acid P-0149 : Combine 4-(3-(cyclobutylmethyl)-1H-pyrrolo[3,2-c]pyridin-6-yl) in DMSO (0.8 ml) -3,5-Dimethylisoxazole ( 96 , 20 mg, 0.071 mmol), 3,5-dichloro-4-fluorobenzoic acid (22 mg, 0.107 mmol) and cesium carbonate (51 mg, 0.16 mmol) And stirred at 85°C for 5 hours. Then, the reactant was filtered through absorbent cotton and partitioned between ethyl acetate and aqueous ammonium chloride. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the material was purified by silica gel flash column chromatography (0 to 10% methanol/DCM) to obtain partially pure material by reverse phase HPLC (C18; 0-100% B; A: 5%) CH ₃ CN, 95% H ₂ O, 0.1% HCO ₂ H; B: 95% CH ₃ CN, 5% H ₂ O, 0.1% HCO ₂ H) was further purified to obtain 3,5-dichloro-4-( 3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-c]pyridin-1-yl)benzoic acid ( P-0149 ). MS (ESI) [M+H ⁺ ] ⁺ = 471.0.

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 439.6 P-0002

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 493.6 P-0003

4-(1-(環戊基(吡啶-2-基)甲基)-3-苯基1H-吡咯并[2,3-b]吡啶-5-基)-3,5-二甲基異噁唑 449.20 P-0004

4-(1-(環己基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 507.2 P-0005

4-(5-(3,5-二甲基異噁唑-4-基)-1-甲苯磺醯基-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸甲酯 502.1 P-0006

4-(5-(3,5-二甲基異噁唑-4-基)-1-甲苯磺醯基-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 488.1 P-0007

4-(1-(環丙基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 465.55 P-0008

4-(1-(環丁基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 479.1 P-0009

6-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)菸鹼酸          403.1 P-0010

6-(3-(環丙基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)菸鹼酸 388.4 P-0011

6-(6-(3,5-二甲基異噁唑-4-基)-3-(吡啶-2-基甲基)-1H-吡咯并[3,2-b]吡啶-1-基)菸鹼酸 425.4 P-0012

4-(1-(二(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 501.5 P-0013

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(嘧啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 439.5 P-0014

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(5-氟吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 456.5 P-0015

3-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 492.6 P-0016

5-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-2-氟苯甲酸 510.6 P-0017

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 493.6 P-0018

2-(3-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯基)乙酸 507.1 P-0019

4-(1-(環戊基(吡啶-2-基)甲基)-3-(吡啶-4-基)-1H-吡咯并[2,3-b]吡啶-5-基)-3,5-二甲基異噁唑 449.5 P-0020

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲醯胺 491.6    P-0021

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-N-甲基苯甲醯胺 506.2 P-0022

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲腈 474.1 P-0023

5-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)異吲哚啉-1-酮 503.6 P-0024

4-(3-(4-(2H-四唑-5-基)苯基)-1-(環戊基(吡啶-2-基)甲基)-1H-吡咯并[2,3-b]吡啶-5-基)-3,5-二甲基異噁唑 517.3 P-0025

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-2-氟苯甲酸 511.3 P-0026

5-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 494.2 P-0027

3-氯-4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 527.2 P-0028

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-2-甲基苯甲酸 507.1 P-0029

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-2-(三氟甲基)苯甲酸    561.1 P-0030

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-2-羥基苯甲酸 509.2 P-0031

2-(4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯基)乙酸       507.1 P-0032

2-(4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯基)-2-甲基丙酸 535.3          P-0033

1-(4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯基)環丙烷-1-甲酸 533.2          P-0034

2-(4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯基)-2,2-二氟乙酸 543.1 P-0035

2-(4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-1H-吡唑-1-基)-2-甲基丙酸 525.4 P-0036

2-(4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-1H-吡唑-1-基)乙酸 497.2 P-0037

1-(4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-1H-吡唑-1-基)-2-甲基丙-2-醇 511.3 P-0038

2-氯-4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 527.2 P-0040

4-(1-(環戊基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸甲酯       508.2 P-0041

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 429.1 P-0042

4-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 425.2 P-0043

4-(1-(環丁基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 480.0 P-0044

4-(5-(3,5-二甲基異噁唑-4-基)-1-(吡啶-2-基甲基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 426.2 P-0045

4-(1-(環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 389.2 P-0046

4-(1-(環丁基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸甲酯 494.2 P-0047

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-甲氧基苯甲酸 469.6 P-0048

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 424.2 P-0049

3-(5-(3,5-二甲基異噁唑-4-基)-1-(吡啶-2-基甲基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 425.2 P-0050

3-(1-(環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 387.4 P-0051

4-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-2,2-二甲基丁-3-炔酸       414.6 P-0052

4-(3-苯甲基-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸甲酯 439.5 P-0053

4-(3-苯甲基-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 425.0 P-0054

4-(3-苯甲醯基-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 439.0 P-0055

4-(5-(3,5-二甲基異噁唑-4-基)-1-(苯基磺醯基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 474.9 P-0056

3-(5-(3,5-二甲基異噁唑-4-基)-1-(3-甲氧基苯甲基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸       454.2 P-0057

4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-甲氧基苯甲基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸       455.2 P-0058

3-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 428.2 P-0059

3-(5-(3,5-二甲基異噁唑-4-基)-1-(3-(三氟甲氧基)苯甲基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 508.2 P-0060

3-(5-(3,5-二甲基異噁唑-4-基)-1-(3-氟苯甲基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 442.2 P-0061

3-(1-(3-氯苯甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸       458.1 P-0062

3-(5-(3,5-二甲基異噁唑-4-基)-1-(3-甲基苯甲基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸    438.2 P-0063

3-(5-(3,5-二甲基異噁唑-4-基)-1-(3-(三氟甲基)苯甲基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 492.1 P-0064

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3-(二氟甲氧基)苯甲酸 468.1 P-0065

4-(3-(環丙基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 389.6 P-0066

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3-(三氟甲氧基)苯甲酸 486.5 P-0067

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二甲氧基苯甲酸 462.1 P-0068

4-(3-(環丁基甲基)-1-(3-氟-4-(甲基磺醯基)苯基)-1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑 454.2 P-0069

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)丙炔酸 372.1 P-0070

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 523.5 P-0071

(S)-3-(二氟甲氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 505.5 P-0072

3-(1-(二環丁基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 456.2 P-0073

3-(1-(環丁基(吡啶-2-基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 479.6 P-0074

3,5-二氯-4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 471.7 P-0075

6-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-5-甲基菸鹼酸 417.1 P-0076

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲腈 383.0 P-0077

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)2-氰吡啶 384.0 P-0078

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-N-氰基苯甲醯胺 448.0 P-0079

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-N-羥基苯甲醯胺 439.0 P-0080

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 439.0 P-0081

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯磺醯胺 459.0       P-0082

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-N-甲基苯磺醯胺 473.0 P-0083

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-N-環丙基苯磺醯胺    499.0 P-0084

4-(3-(環丙烷羰基)-6-(3,5-二甲基異噁唑-4-基)-2-羥基-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 419.0 P-0085

3-(1-苯甲醯基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 438.0 P-0086

4-溴-2-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3-氟苯甲酸 499.9 P-0087

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-2-氟-3-甲氧基苯甲酸 450.1 P-0088

4-(3-(3-氯苯甲醯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 472.9 P-0089

4-(3-(2-氯苯甲醯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 473.4 P-0090

4-(3-(3-氯苯甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 459.0 P-0091

4-(3-(2-氯苯甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 459.1 P-0092

3-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-N-(甲基磺醯基)苯甲醯胺 501.1 P-0093

4-(1-苯甲基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)環己-3-烯-1-甲酸 428.1 P-0094

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二氟苯甲酸 475.5 P-0095

3,5-二氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 507.1 (MH)- P-0096

N-(3-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-2,4-二氟苯基)甲烷磺醯胺 524.5    P-0097

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-氟苯甲酸 457.3 P-0098

3-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-4-甲氧基苯甲酸 432.1 P-0099

4-(3-(3-(二氟甲氧基)苯甲醯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 505.1    P-0100

4-(3-(3-(二氟甲氧基)苯甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶甲酸 491.0 P-0101

3-(1-((3,3-二氟環丁基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 438.1 P-0102

3-(5-(3,5-二甲基異噁唑-4-基)-1-((3-甲基氧雜環丁-3-基)甲基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 418.1 P-0103

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二甲氧基苯甲酸 499.1 P-0104

2-氰基-5-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 427.1 P-0105

2-氰基-4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 427.1 P-0106

(S)-6-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)吡嗪-2-甲酸 441.1 P-0107

(S)-2-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)嘧啶-4-甲酸 441.1 P-0108

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3-乙氧基-5-氟苯甲酸 464.6 P-0109

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 490.2    P-0110

7-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯并呋喃-4-甲酸 442.1       P-0111

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二異丙氧基苯甲酸 518.2 P-0112

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 497.1 P-0113

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-丙氧基苯甲酸 497.1 P-0114

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-乙氧基苯甲酸 483.1 P-0115

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2,2-三氟乙氧基)苯甲酸 537.6 P-0116

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲基)苯甲酸 507.5 P-0117

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二丙氧基苯甲酸 555.6 P-0118

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二異丙氧基苯甲酸 555.6 P-0119

4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-苯基乙基)-1H-吡咯并[3,2-b]吡啶-3-基)-3,5-二甲氧基苯甲酸 498.6 P-0120

2-(6-(3,5-二甲基異噁唑-4-基)-1-(1-苯基乙基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 438.6 P-0121

3,5-二氯-4-(3-(環丁烷羰基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 485.0 P-0122

6-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶甲酸 440.2 P-0123

6-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)菸鹼酸 439.5 P-0124

2-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)異菸鹼酸 440.2 P-0125

(S)-3-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-2,6-二氟苯甲酸 475.3 P-0126

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)嘧啶-2-甲酸 441.1 P-0127

4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二丙氧基苯甲酸 518.2 P-0128

3,5-二氯-4-(3-(3-氯苯甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 525.9 (MH)-    P-0129

3,5-二氯-4-(3-(3-(二氟甲氧基)苯甲醯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 572.1 (MH)- P-0130

4-(3-(環丁基甲基)-1-(2-氟-4-硝基苯基)-1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑 421.3 P-0131

3,5-二氯-4-(3-(2-氯苯甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 526.0 (MH)- P-0132

4-(3-(3-(苯甲氧基)苯甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二氯苯甲酸 598.1 (MH)- P-0133

4-(3-(3-(苯甲氧基)苯甲醯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二氯苯甲酸 612.0 (MH)-    P-0134

4-(3-(環丁基甲基)-1-(6-甲氧基吡啶-3-基)-1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑 389.6    P-0135

(S)-3-(苯甲氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-甲氧基苯甲酸 575.1 P-0136

3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-苯基乙基)-1H-吡咯并[3,2-b]吡啶-3-基)-2-甲氧基苯甲酸 468.6 P-0137

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(氧雜環丁-3-基氧基)苯甲酸       511.5 P-0138

(S)-3-(環丙基甲氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 509.6 P-0139

(S)-3-(苯甲氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 545.5 P-0140

3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-苯基乙基)-1H-吡咯并[3,2-b]吡啶-3-基)-4-甲氧基苯甲酸 468.6 P-0141

4-氯-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-苯基乙基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 473.0 P-0142

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[3,2-b]吡啶-3-基)-3-甲氧基苯甲酸 469.6 P-0143

5-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)吡啶-2-醇 375.2 P-0144

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-羥基-5-甲氧基苯甲酸 485.6 P-0145

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)吡啶-2-醇 412.2          P-0146

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[3,2-b]吡啶-3-基)-3,5-二甲氧基苯甲酸 499.6 P-0147

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二乙氧基苯甲酸 527.6 P-0148

(S)-4-氯-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)丙基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 487.5 P-0149

3,5-二氯-4-(3-(環丁基甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-c]吡啶-1-基)苯甲酸 471.0 P-0150

3,5-二氯-4-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 478.0 P-0151

3,5-二氯-4-(3-(3,6-二氫-2H-哌喃-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)苯甲酸 485.7 P-0152

(S)-3-(環丙基甲氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-甲氧基苯甲酸 539.6 P-0153

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-甲氧基-5-(2,2,2-三氟乙氧基)苯甲酸 566.5 P-0154

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 507.1 P-0155

4-(3-(2-氯苯基)-1-(1,1-二(吡啶-2-基)乙基)-1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑       506.1 P-0156

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 512.1 P-0157

4-(1-((3,3-二氟環丁基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 522.5 P-0158

4-(5-(3,5-二甲基異噁唑-4-基)-1-(吡啶-2-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 495.5 P-0159

4-(6-(3,5-二甲基異噁唑-4-基)-3-(吡啶-2-基甲基)-1H-吡咯并[3,2-b]吡啶-1-基)-3-(三氟甲氧基)苯甲酸 509.5 P-0160

(S)-3,5-二甲基-4-(3-(1-甲基-1H-吡唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-6-基)異噁唑 467.6 P-0161

(S)-2-(3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)苯基)乙酸 521.6 P-0162

(S)-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 507.5 P-0163

4-(3-(二環丙基(羥基)甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3-(三氟甲氧基)苯甲酸 528.1 P-0164

4-氯-3-(1-(1,1-二(吡啶-2-基)乙基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 550.1 P-0165

4-(3-(二環丙基(羥基)甲基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 532.2 P-0166

4-氰基-3-(1-(1,1-二(吡啶-2-基)乙基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 541.1 P-0167

4-(1-(1,1-二(吡啶-2-基)乙基)-3-(2-乙炔基苯基)-1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑 496.6 P-0168

4-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 498.6 P-0169

2-(1-(1,1-二(吡啶-2-基)乙基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲腈 497.1 P-0170

(S)-3-環丙氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸       495.6 P-0171

(S)-3-(環丙基乙炔基)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸    503.6 P-0172

3-(1-(1,1-二(吡啶-2-基)乙基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-3-基)-4-甲氧基苯甲酸 546.6 P-0173

4-(6-(3,5-二甲基異噁唑-4-基)-3-(吡啶-3-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 499.1 P-0174

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-乙氧基-5-異丙氧基苯甲酸    P-0175

4-(5-(3,5-二甲基異噁唑-4-基)-1-(吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 495.0 P-0176

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-甲氧基吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 525.0 P-0177

4-(1-(4-氯吡啶-3-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 529.0 P-0178

(S)-3-(環丙基乙炔基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 503.2 P-0179

(S)-3-環丁氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 509.1    P-0180

4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-(三氟甲基)吡啶-2-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 563.1             P-0181

(S)-3-環丙基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 479.1 P-0182

4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-氟吡啶-2-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 513.1 P-0183

4-(1-(3-氯吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 529.5 P-0184

4-(6-(3,5-二甲基異噁唑-4-基)-3-(4-氟苯基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 516.1 P-0185

4-(3-(3-氯苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 532.1 P-0186

4-(3-(2,4-二氟苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 534.1 P-0187

4-(6-(3,5-二甲基異噁唑-4-基)-3-(吡啶-2-基甲基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 513.2 P-0188

4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 494.1 P-0189

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-甲基吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 509.5 P-0190

4-(3-(環丁基甲基)-6-(1,4-二甲基-1H-1,2,3-三唑-5-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 490.1 P-0191

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-(N-嗎啉基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 531.5 P-0192

4-(3-(6-環丙基吡啶-3-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 539.6 P-0193

4-(3-(5-氯吡啶-3-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 533.1    P-0194

4-(6-(3,5-二甲基異噁唑-4-基)-3-(2-氟-4-甲氧基苯基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸    P-0195

4-(6-(3,5-二甲基異噁唑-4-基)-3-(1-甲基-1H-吡唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 502.6 P-0196

4-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-3-(三氟甲氧基)苯甲酸    494.0 P-0197

(S)-3,5-二氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 507.1 P-0198

3-氯-4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 546.1 P-0199

4-(1-(2-氰基-1-環丙基乙基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 511.1 P-0200

4-(1-(2-氰基-1-環戊基乙基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸       539.1 P-0201

4-(6-(3,5-二甲基異噁唑-4-基)-3-(2-甲氧基嘧啶-5-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 530.2 P-0202

4-(1-(環丙基磺醯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 522.0 P-0203

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-異丙基吡啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 537.5 P-0204

4-(1-(4-氰基吡啶-3-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 520.1 P-0205

4-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-3-乙氧基-5-氟苯甲酸 472.1 P-0206

2-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-3-乙氧基苯甲腈 435.1 P-0207

3-氯-2-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)苯甲腈 425.0 P-0208

4-(3-(4,4-二氟環己-1-烯-1-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 538.6 P-0209

4-(3-(3-氯-4-氟苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 550.1 P-0210

4-(3-(環丁基甲基)-6-(3-(甲氧基甲基)-5-甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 520.1 P-0211

4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-甲基吡啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 509.1 P-0212

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1,1-二氧離子基四氫-2H-硫哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 550.1 P-0213

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 486.2 P-0214

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2,2-三氟乙氧基)苯甲酸 526.1 P-0215

4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 520.1 P-0216

4-(1-(3-(環丙基乙炔基)吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 559.1 P-0217

4-(3-(4-氰基-2-氟苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸       541.2 P-0218

4-(3-(4-(環丙基胺甲醯基)苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 581.2 P-0219

4-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二甲氧基苯甲酸甲酯 484.1 P-0220

4-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二甲氧基苯甲酸 470.1 P-0221

4-(1-(2,6-二甲氧基苯基)-3-苯基1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑 426.6 P-0222

4-(6-(3,5-二甲基異噁唑-4-基)-3-(2-氟吡啶-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 517.1 P-0223

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-氟苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 512.1 P-0224

4-(1-(2-氯-6-乙氧基苯基)-3-苯基1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑 444.0 P-0225

3-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-4-乙氧基苯甲酸 454.1 P-0226

4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 502.1 P-0227

4-(1-(4,4-二氟環己基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 536.1 P-0228

4-(5-(3,5-二甲基異噁唑-4-基)-2-甲基-1-(吡啶-2-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 509.1 P-0229

4-(3-(2,4-二氟苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3-(三氟甲氧基)苯甲酸 530.1 P-0230

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-氟-5-(三氟甲氧基)苯甲酸 530.1 P-0231

4-(5-(3,5-二甲基異噁唑-4-基)-1-(鄰甲苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 508.1 P-0232

4-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 530.1 P-0233

4-(1-(2,5-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 530.0 P-0234

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-3-氟苯甲酸 525.4 P-0235

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-3-甲基苯甲酸 521.2 P-0236

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-3-甲氧基苯甲酸 537.4    P-0237

(S)-4-(3-(3-環丙基-1-甲基-1H-吡唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-6-基)-3,5-二甲基異噁唑 507.1    P-0238

(S)-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-4-氟苯甲酸 525.4 P-0239

(S)-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-4-甲氧基苯甲酸 537.4 P-0240

(S)-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-5-氟苯甲酸 525.4 P-0241

(S)-3-氯-5-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 541.3 P-0242

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-2-氟苯甲酸 521.2    P-0243

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-2-甲基苯甲酸 521.2    P-0244

(S)-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-2-甲氧基苯甲酸 537.4    P-0245

(S)-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-2-氟苯甲酸 525.4 P-0246

(S)-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)-2-甲基苯甲酸 521.2 P-0247

(S)-2-氯-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 541.3 P-0248

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-乙氧基-2-羥基苯甲酸甲酯 534.2 P-0249

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-乙氧基-2-羥基苯甲酸 506.1 P-0250

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-乙氧基-2-甲氧基苯甲酸 520.1 P-0251

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-氟吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 513.1 P-0252

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-羥基吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 511.1 P-0253

4-(1-(3-氯吡啶-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 529.0 P-0254

4-(1-(2-氰基-6-氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 537.1 P-0255

4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)-3-甲氧基-5-甲基苯甲酸 454.1 P-0256

(S)-3-氰基-4-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 532.3 P-0257

(S)-4-氯-3-(6-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-2-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸 541.3 P-0258

4-(6-(3,5-二甲基異噁唑-4-基)-3-(1-((甲基磺醯基)甲基)-1H-吡唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 580.3 P-0259

4-(6-(3,5-二甲基異噁唑-4-基)-3-(1-異丙基-3-甲基-1H-吡唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 544.3 P-0260

4-(6-(3,5-二甲基異噁唑-4-基)-3-(1-(2-羥基-2-甲基丙基)-1H-吡唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸       560.2 P-0261

4-(3-(1-(二氟甲基)-1H-吡唑-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 538.6 P-0262

4-(3-(1-(2-(二甲基胺基)乙基)-1H-吡唑-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 559.3 P-0263

4-(3-(1,3-二甲基-1H-吡唑-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 516.4 P-0264

4-(3-(1-(環丙基甲基)-1H-吡唑-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 542.5 P-0265

4-(3-(1-環丙基-1H-吡唑-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 528.4 P-0266

4-(3-(1-(2-氰基乙基)-1H-吡唑-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 541.3 P-0267

4-(3-(1-(2-(二甲基胺基)-2-側氧基乙基)-1H-吡唑-4-基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 573.4 P-0268

3-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-(三氟甲氧基)苯甲酸 530.1 P-0269

4-(3-(2,4-二氟苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二異丙氧基苯甲酸 562.1 P-0270

4-(3-(環丁基甲基)-6-(3,5-二甲基-4H-1,2,4-三唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 490.1 P-0271

4-(3-(4,4-二氟環己基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-3,5-二乙氧基苯甲酸 540.1 P-0272

2-(4-(1-(3-(環丙基乙炔基)吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-1H-吡唑-1-基)乙酸 479.2 P-0273

3-(二氟甲氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 476.1 P-0274

3-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-4-(三氟甲氧基)苯甲酸 494.0 P-0275

4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 468.1 P-0276

3-環丁氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 480.1 P-0277

3-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 490.1 P-0278

4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2,2-三氟乙氧基)苯甲酸 508.1 P-0279

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-氟苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 512.0 P-0280

2-(4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-1H-吡唑-1-基)乙酸 432.2 P-0281

4-(1-(2-(氮雜環丁-1-基)嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 551.1 P-0282

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-(甲基磺醯基)苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 572.0 P-0283

3-氯-4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-異丙氧基苯甲酸 520.2 P-0284

3-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-(三氟甲氧基)苯甲酸 512.1 P-0285

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 488.1 P-0286

(R)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 488.1 P-0287

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-乙基-3-甲基-1H-吡唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 526.1 P-0288

4-(1-(1-(二氟甲基)-3-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 548.1 P-0289

4-(1-(1-(二氟甲基)-5-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 548.1 P-0290

4-(5-(3,5-二甲基異噁唑-4-基)-1-(哌啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 501.1 P-0291

4-(1-(1-乙醯基哌啶-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 543.1 P-0292

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(甲基磺醯基)哌啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 579.1 P-0293

4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-氟吡啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸       513.1 P-0294

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(2-羥基-2-甲基丙基)-1H-吡唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 556.1 P-0295

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-乙氧基吡啶甲酸 491.1 P-0296

4-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二乙氧基-2,6-二氟苯甲酸 570.1 P-0297

4-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二乙氧基-2-氟苯甲酸 552.1 P-0298

4-(6-(3,5-二甲基異噁唑-4-基)-3-苯基1H-吡咯并[3,2-b]吡啶-1-基)-3,5-雙(2,2,2-三氟乙氧基)苯甲酸 606.1 P-0299

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(2-羥基-2-甲基丙基)-1H-吡唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 530.2 P-0300

4-(1-(2-(氮雜環丁-1-基)嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 525.1 P-0301

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 462.1 P-0302

4-(3-(2-異丙氧基-4-(甲基磺醯基)苯基)-1-苯基1H-吡咯并[2,3-b]吡啶-5-基)-3,5-二甲基異噁唑 502.1 P-0303

4-胺基-5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-1-丙基-1H-吡唑-3-甲酸 493.1 P-0304

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-(乙基胺基)-1-丙基-1H-吡唑-3-甲酸 521.2 P-0305

(E)-4-(1-(4-環丙基丁-3-烯-1-基)-5-(1,4-二甲基-1H-1,2,3-三唑-5-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 512.1 P-0306

4-(1-(3-氯吡啶-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2-二氟乙氧基)苯甲酸 525.1 P-0307

4-(1-(2-氯苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 528.1 P-0308

4-(1-(2-環丙基苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 534.1 P-0309

4-(1-(2-氰基苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 519.4 P-0310

4-(1-(4-氰基-2-甲基苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 533.2 P-0311

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-氟-4-甲氧基苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 542.2 P-0312

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-(丙-1-烯-2-基)苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 534.1 P-0313

4-(1-(4-氰基苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 519.1 P-0314

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-(2-羥基丙-2-基)苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 552.4 P-0315

4-(5-(3,5-二甲基異噁唑-4-基)-1-(噻吩-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 500.2 P-0316

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-甲氧基吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 525.4 P-0317

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-甲基吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 509.2       P-0318

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-甲基-1H-吡唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 498.4 P-0319

4-(5-(3,5-二甲基異噁唑-4-基)-1-(嘧啶-5-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 496.3 P-0320

4-(1-(2-胺基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 511.3 P-0321

4-(1-(2-(二甲基胺基)嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 539.5 P-0322

4-(1-(4-羧基苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 538.3    P-0323

4-(1-(4-胺甲醯基苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸    P-0324

5-(1-(3-氯吡啶-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-甲氧基吡啶甲酸 476.0 P-0325

(S)-3-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 484.0 P-0326

3-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-乙基-3-甲基-1H-吡唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 522.1 P-0327

3-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)-5-氟苯甲酸 508.1 P-0328

4-(1-(2-(氮雜環丁-1-基)嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2-二氟乙氧基)苯甲酸 547.2 P-0329

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 535.2 P-0330

4-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 508.1 P-0331

4-(1-(2-(氮雜環丁-1-基)嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-氯-5-(2,2-二氟乙氧基)苯甲酸 581.1 P-0332

3-氯-5-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-苯基1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 524.0    P-0333

(S)-3-氯-5-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 518.1 P-0334

4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-環丁氧基苯甲酸 506.2 P-0335

4-(1-(1-(氰基甲基)環丁基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 511.0 P-0336

4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 494.0 P-0337

4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-環丙氧基苯甲酸 492.0 P-0338

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2-二氟乙氧基)苯甲酸 508.2 P-0339

5-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-甲氧基吡啶甲酸 459.2 P-0340

3-氯-4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(2,2-二氟乙氧基)苯甲酸 542.1 P-0341

3-環丁氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 488.2 P-0342

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-2-甲基-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 500.2 P-0343

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-2-甲基-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 526.1 P-0344

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吲哚-3-基)-3-(三氟甲氧基)苯甲酸 511.1 P-0345

4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-2-甲基-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 534.0 P-0346

(S)-3-氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 522.1 P-0347

4-(1-(2-(氮雜環丁-1-基)嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-環丁氧基苯甲酸 537.1 P-0348

4-(1-(2-(氮雜環丁-1-基)嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2-二氟乙氧基)-5-氟苯甲酸 565.1 P-0349

3-(2,2-二氟乙氧基)-4-(1-(1-(二氟甲基)-3-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 544.0 P-0350

(S)-3-環丁氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 474.2 P-0351

3-環丁氧基-4-(1-(1-(二氟甲基)-3-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 534.1 P-0352

3-氯-5-(2,2-二氟乙氧基)-4-(1-(1-(二氟甲基)-5-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸       578.0 P-0353

3-環丁氧基-4-(1-(1-(二氟甲基)-5-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 534.1 P-0354

4-(1-(1-(二氟甲基)-5-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 520.0 P-0355

3-氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 536.1 P-0356

3-氯-5-環丁氧基-4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 532.2 P-0357

4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 476.2 P-0358

3-氯-5-環丁氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 522.1 P-0359

3-氯-5-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 532.0 P-0360

(S)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 466.1 P-0361

(S)-3-氯-5-環丁氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 508.1 P-0362

5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-甲氧基吡啶甲酸 449.2 P-0363

3-氯-5-環丙氧基-4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 518.1 P-0364

4-(1-((1-氰基環丁基)甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 511.2 P-0365

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(2-羥基-2-甲基丙基)-3-甲基-1H-吡唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 570.2 P-0366

4-(1-(1-(2-(二甲基胺基)-2-側氧基乙基)-3-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 583.2 P-0367

3-(2,2-二氟乙氧基)-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-甲基苯甲酸 512.1 P-0368

5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-甲氧基吡啶甲酸 449.2 P-0369

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-氟-5-異丙氧基苯甲酸 504.2 P-0370

3-氯-4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基苯甲酸 506.2 P-0371

3-氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基苯甲酸 496.2 P-0372

3-氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-異丙氧基苯甲酸       510.2 P-0373

5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 507.2 P-0374

4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3,5-二乙氧基-2-氟苯甲酸 524.2 P-0375

4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 480.2 P-0376

5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基吡啶甲酸 463.2       P-0377

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-氟苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 490.1 P-0378

4-(1-環丁基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 472.1 P-0379

3-環丙氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 474.5 P-0380

3-氯-4-(1-(二環丁基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 574.1 P-0381

3-氯-5-環丙氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 508.1 P-0382

4-(1-環戊基-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 486.1       P-0383

4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-甲基四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 502.0 P-0384

4-(1-(2-環丙基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 536.1          P-0385

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-甲基四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 516.0 P-0386

3-氯-4-(1-(2-環丙基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 570.1 P-0387

4-(1-(2-環丙基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(2,2-二氟乙氧基)苯甲酸 532.2 P-0388

4-(1-(6-環丙基吡啶-3-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 535.2 P-0389

4-(1-(3-氰基環戊基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 511.1 P-0390

3-氯-4-(1-(2-環丙基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(2,2-二氟乙氧基)苯甲酸 566.1    P-0391

3-氯-5-環丁氧基-4-(1-(2-環丙基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 556.1 P-0392

4-(5-(3,5-二甲基異噁唑-4-基)-1-(2-甲氧基嘧啶-5-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 526.1 P-0393

3-氯-4-(1-(2-環丙基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-異丙氧基苯甲酸 544.1       P-0394

3-環丙氧基-4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-氟苯甲酸 502.2 P-0395

3-氯-4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 554.1 P-0396

3-氯-4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-環丁氧基苯甲酸 540.0 P-0397

3-環丙氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-氟苯甲酸 492.2 P-0398

3-氯-5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基吡啶甲酸 497.1 P-0399

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-甲基-6-側氧基-1,6-二氫吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 525.1 P-0400

4-(5-(3-乙基-5-甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 516.1 P-0401

4-(5-(5-乙基-3-甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-(三氟甲氧基)苯甲酸 516.1 P-0402

4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基-5-甲基苯甲酸 490.1 P-0403

4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-甲基四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 490.2 P-0404

3-氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(4-甲基四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-異丙氧基苯甲酸 524.2 P-0405

5-(5-(3,5-二甲基異噁唑-4-基)-1-(4-甲基四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基吡啶甲酸 477.1 P-0406

(S)-3-氯-5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基吡啶甲酸 483.1 P-0407

4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-甲基四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-異丙氧基苯甲酸 476.1 P-0408

3-氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(3-甲基四氫呋喃-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-異丙氧基苯甲酸 510.1 P-0409

3-氯-4-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-環丙氧基苯甲酸 526.1 P-0410

3-環丁氧基-4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-氟苯甲酸 506.2 P-0411

5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基-4-甲基吡啶甲酸 477.2 P-0412

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基-4-甲基吡啶甲酸 505.2 P-0413

3-環丙氧基-4-(5-(1,4-二甲基-1H-1,2,3-三唑-5-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 Insert P-0414

5-(5-(3,5-二甲基異噁唑-4-基)-1-(2-氟苯基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸    517.2 P-0415

(S)-5-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 528.2 P-0416

5-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基-3-甲基吡啶甲酸 487.2 P-0417

5-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-6-乙氧基-4-甲基吡啶甲酸 487.2 P-0418

4-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-甲基吡啶甲酸 443.2 P-0419

4-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-甲基吡啶甲酸 433.2 P-0420

5-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 517.2 P-0421

5-(1-(3-氰基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 525.1 P-0422

5-(1-(3-胺甲醯基吡啶-2-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 543.2 P-0423

5-(1-(4-氰基-2-氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 542.2 P-0424

5-(1-(2-環丙基嘧啶-5-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 541.2 P-0425

5-(1-(4,4-二氟環己基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸    541.2 P-0426

5-(1-(6-環丙基吡啶-3-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 540.2 P-0427

5-(1-(二環丙基甲基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-乙氧基吡啶甲酸 473.2 P-0428

5-(5-(3,5-二甲基異噁唑-4-基)-1-(四氫-2H-哌喃-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-乙氧基吡啶甲酸 463.2 P-0429

5-(1-(1-(二氟甲基)-3-甲基-1H-吡唑-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 553.2 P-0430

5-(5-(3,5-二甲基異噁唑-4-基)-1-(1-乙基-3-甲基-1H-吡唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 531.2 P-0431

5-(3-(2,4-二氟苯基)-6-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[3,2-b]吡啶-1-基)-4,6-二乙氧基吡啶甲酸 535.2 P-0432

5-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸甲酯 549.2 P-0433

5-(1-(1-(第三丁氧基羰基)哌啶-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 606.3 P-0434

4-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)環己烷-1-甲酸 452.2 P-0435

5-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(甲基磺醯基)哌啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 584.2 P-0436

5-(5-(3,5-二甲基異噁唑-4-基)-1-(吡啶-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4,6-二乙氧基吡啶甲酸 500.0 P-0437

2-(4-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-3-氟苯基)乙酸 478.1 P-0438

2-(4-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)苯基)乙酸 460.1 P-0439

3-氯-4-(5-(3,5-二甲基異噁唑-4-基)-1-(噠嗪-3-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 530.1 P-0440

3-氯-4-(1-(6-環丙基吡啶-3-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸甲酯 583.1 P-0441

3-氯-4-(1-(6-環丙基吡啶-3-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 569.1 P-0442

4-(1-(1-(第三丁氧基羰基)哌啶-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 579.3 P-0443

2-(3-(1-(2,4-二氟苯基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-4-甲氧基苯基)乙酸 490.1 P-0444

4-(1-(6-環丙基吡啶-3-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-2-氟-5-(三氟甲氧基)苯甲酸 553.2 P-0445

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-特戊醯基哌啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 563.3 P-0446

4-(1-(1-(2-氰基乙基)哌啶-4-基)-5-(3,5-二甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 532.2 P-0447

4-(5-(3,5-二甲基異噁唑-4-基)-1-(1-(2-羥基乙醯基)哌啶-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-乙氧基-2-氟苯甲酸 537.2 P-0448

3-氯-4-(1-(6-環丙基吡啶-3-基)-5-(5-乙基-3-甲基異噁唑-4-基)-1H-吡咯并[2,3-b]吡啶-3-基)-5-(三氟甲氧基)苯甲酸 583.2 P-0449

(S)-3-(5-(1,4-二甲基-1H-1,2,3-三唑-5-基)-1-(1-(吡啶-2-基)乙基)-1H-吡咯并[2,3-b]吡啶-3-基)苯甲酸 439.1    生物實例 生物測試方法 使用以下分析法測試本發明之化合物： EP300 Alphascreen 結合分析法 All the compounds in Table 1 listed below can be prepared according to the synthesis examples described in the present invention and by performing any necessary substitution of starting materials that can be obtained commercially or otherwise by those skilled in the art.table 1 P# structure name (MH)+ P-0001

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)benzoic acid 439.6 P-0002

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzoic acid 493.6 P-0003

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-3-phenyl 1H-pyrrolo[2,3-b]pyridin-5-yl)-3,5-dimethyliso Oxazole 449.20 P-0004

4-(1-(Cyclohexyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)benzoic acid 507.2 P-0005

Methyl 4-(5-(3,5-dimethylisoxazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoate 502.1 P-0006

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 488.1 P-0007

4-(1-(Cyclopropyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzoic acid 465.55 P-0008

4-(1-(Cyclobutyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzoic acid 479.1 P-0009

6-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)nicotinic acid 403.1 P-0010

6-(3-(Cyclopropylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl) smoke Alkaline Acid 388.4 P-0011

6-(6-(3,5-Dimethylisoxazol-4-yl)-3-(pyridin-2-ylmethyl)-1H-pyrrolo[3,2-b]pyridin-1-yl ) Niacin 425.4 P-0012

4-(1-(Bis(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)benzoic acid 501.5 P-0013

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyrimidin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)benzoic acid 439.5 P-0014

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(5-fluoropyridin-2-yl)ethyl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)benzoic acid 456.5 P-0015

3-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzoic acid 492.6 P-0016

5-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)-2-fluorobenzoic acid 510.6 P-0017

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)picolinic acid 493.6 P-0018

2-(3-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)phenyl)acetic acid 507.1 P-0019

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3, 5-Dimethylisoxazole 449.5 P-0020

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzamide 491.6 P-0021

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)-N-methylbenzamide 506.2 P-0022

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzonitrile 474.1 P-0023

5-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl) isoindolin-1-one 503.6 P-0024

4-(3-(4-(2H-tetrazol-5-yl)phenyl)-1-(cyclopentyl(pyridin-2-yl)methyl)-1H-pyrrolo[2,3-b] (Pyridin-5-yl)-3,5-dimethylisoxazole 517.3 P-0025

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)-2-fluorobenzoic acid 511.3 P-0026

5-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)picolinic acid 494.2 P-0027

3-chloro-4-(1-(cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)benzoic acid 527.2 P-0028

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)-2-methylbenzoic acid 507.1 P-0029

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] Pyridin-3-yl)-2-(trifluoromethyl)benzoic acid 561.1 P-0030

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)-2-hydroxybenzoic acid 509.2 P-0031

2-(4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)phenyl)acetic acid 507.1 P-0032

2-(4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)phenyl)-2-methylpropionic acid 535.3 P-0033

1-(4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)phenyl)cyclopropane-1-carboxylic acid 533.2 P-0034

2-(4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)phenyl)-2,2-difluoroacetic acid 543.1 P-0035

2-(4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropionic acid 525.4 P-0036

2-(4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-1H-pyrazol-1-yl)acetic acid 497.2 P-0037

1-(4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol 511.3 P-0038

2-Chloro-4-(1-(cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)benzoic acid 527.2 P-0040

4-(1-(Cyclopentyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] Pyridin-3-yl) methyl picolinate 508.2 P-0041

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) Picolinic acid 429.1 P-0042

4-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinic acid 425.2 P-0043

4-(1-(Cyclobutyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)picolinic acid 480.0 P-0044

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl )Picolinic acid 426.2 P-0045

4-(1-(Cyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridine Formic acid 389.2 P-0046

4-(1-(Cyclobutyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] Pyridin-3-yl) methyl picolinate 494.2 P-0047

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-methoxybenzoic acid 469.6 P-0048

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 424.2 P-0049

3-(5-(3,5-Dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl )benzoic acid 425.2 P-0050

3-(1-(Cyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzene Formic acid 387.4 P-0051

4-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2- Dimethyl but-3-ynoic acid 414.6 P-0052

Methyl 4-(3-benzyl-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)picolinate 439.5 P-0053

4-(3-Benzyl-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)picolinic acid 425.0 P-0054

4-(3-Benzyl-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)picolinic acid 439.0 P-0055

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridine Formic acid 474.9 P-0056

3-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine-3- Base) benzoic acid 454.2 P-0057

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)picolinic acid 455.2 P-0058

3-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) benzoic acid 428.2 P-0059

3-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-(trifluoromethoxy)benzyl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzoic acid 508.2 P-0060

3-(5-(3,5-dimethylisoxazol-4-yl)-1-(3-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl) benzoic acid 442.2 P-0061

3-(1-(3-Chlorobenzyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) benzoic acid 458.1 P-0062

3-(5-(3,5-dimethylisoxazol-4-yl)-1-(3-methylbenzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl )benzoic acid 438.2 P-0063

3-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)benzoic acid 492.1 P-0064

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3- (Difluoromethoxy)benzoic acid 468.1 P-0065

4-(3-(Cyclopropylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridine Formic acid 389.6 P-0066

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3- (Trifluoromethoxy)benzoic acid 486.5 P-0067

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3, 5-Dimethoxybenzoic acid 462.1 P-0068

4-(3-(cyclobutylmethyl)-1-(3-fluoro-4-(methylsulfonyl)phenyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-3 ,5-Dimethylisoxazole 454.2 P-0069

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)propioic acid 372.1 P-0070

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 523.5 P-0071

(S)-3-(Difluoromethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl )-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 505.5 P-0072

3-(1-(Dicyclobutylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 456.2 P-0073

3-(1-(Cyclobutyl(pyridin-2-yl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)benzoic acid 479.6 P-0074

3,5-Dichloro-4-(3-(cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine- 1-yl)benzoic acid 471.7 P-0075

6-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-5- Methyl nicotinic acid 417.1 P-0076

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)benzonitrile 383.0 P-0077

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)2-cyano Pyridine 384.0 P-0078

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-cyano Benzamide 448.0 P-0079

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-hydroxybenzene Formamide 439.0 P-0080

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)benzoic acid 439.0 P-0081

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzenesulfonamide 459.0 P-0082

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-methyl Benzenesulfonamide 473.0 P-0083

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-cyclopropyl Benzenesulfonamide 499.0 P-0084

4-(3-(Cyclopropanecarbonyl)-6-(3,5-dimethylisoxazol-4-yl)-2-hydroxy-1H-pyrrolo[3,2-b]pyridin-1-yl )Picolinic acid 419.0 P-0085

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 438.0 P-0086

4-bromo-2-(3-(cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl )-3-fluorobenzoic acid 499.9 P-0087

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-2- Fluoro-3-methoxybenzoic acid 450.1 P-0088

4-(3-(3-Chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl )Picolinic acid 472.9 P-0089

4-(3-(2-Chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl )Picolinic acid 473.4 P-0090

4-(3-(3-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl) Picolinic acid 459.0 P-0091

4-(3-(2-Chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl) Picolinic acid 459.1 P-0092

3-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-(form Sulfonyl) benzamide 501.1 P-0093

4-(1-Benzyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclohex-3- Ene-1-carboxylic acid 428.1 P-0094

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3,5-difluorobenzoic acid 475.5 P-0095

3,5-Dichloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[ 2,3-b)pyridin-3-yl)benzoic acid 507.1 (MH)- P-0096

N-(3-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-2,4-difluorophenyl)methanesulfonamide 524.5 P-0097

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-fluorobenzoic acid 457.3 P-0098

3-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-4- Methoxybenzoic acid 432.1 P-0099

4-(3-(3-(Difluoromethoxy)benzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b ]Pyridin-1-yl)picolinic acid 505.1 P-0100

4-(3-(3-(Difluoromethoxy)benzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b] (Pyridin-1-yl)picolinic acid 491.0 P-0101

3-(1-((3,3-Difluorocyclobutyl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)benzoic acid 438.1 P-0102

3-(5-(3,5-dimethylisoxazol-4-yl)-1-((3-methyloxetan-3-yl)methyl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)benzoic acid 418.1 P-0103

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3,5-dimethoxybenzoic acid 499.1 P-0104

2-cyano-5-(3-(cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Base) benzoic acid 427.1 P-0105

2-cyano-4-(3-(cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Base) benzoic acid 427.1 P-0106

(S)-6-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)pyrazine-2-carboxylic acid 441.1 P-0107

(S)-2-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)pyrimidine-4-carboxylic acid 441.1 P-0108

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3- Ethoxy-5-fluorobenzoic acid 464.6 P-0109

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3, 5-diethoxy benzoic acid 490.2 P-0110

7-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)benzofuran -4-formic acid 442.1 P-0111

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3, 5-Diisopropoxybenzoic acid 518.2 P-0112

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-isopropoxybenzoic acid 497.1 P-0113

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-propoxybenzoic acid 497.1 P-0114

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-ethoxybenzoic acid 483.1 P-0115

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-(2,2,2-trifluoroethoxy)benzoic acid 537.6 P-0116

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-(trifluoromethyl)benzoic acid 507.5 P-0117

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3,5-dipropoxybenzoic acid 555.6 P-0118

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3,5-diisopropoxybenzoic acid 555.6 P-0119

4-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-phenylethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl) -3,5-Dimethoxybenzoic acid 498.6 P-0120

2-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-phenylethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl) benzoic acid 438.6 P-0121

3,5-Dichloro-4-(3-(cyclobutanecarbonyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine -1-yl)benzoic acid 485.0 P-0122

6-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)picolinic acid 440.2 P-0123

6-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl) nicotinic acid 439.5 P-0124

2-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)isonicotinic acid 440.2 P-0125

(S)-3-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-2,6-difluorobenzoic acid 475.3 P-0126

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)pyrimidine-2-carboxylic acid 441.1 P-0127

4-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3, 5-dipropoxybenzoic acid 518.2 P-0128

3,5-Dichloro-4-(3-(3-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b ]Pyridin-1-yl)benzoic acid 525.9 (MH)- P-0129

3,5-Dichloro-4-(3-(3-(difluoromethoxy)benzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrole And [3,2-b]pyridin-1-yl)benzoic acid 572.1 (MH)- P-0130

4-(3-(cyclobutylmethyl)-1-(2-fluoro-4-nitrophenyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethyl Isoxazole 421.3 P-0131

3,5-Dichloro-4-(3-(2-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b ]Pyridin-1-yl)benzoic acid 526.0 (MH)- P-0132

4-(3-(3-(benzyloxy)benzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine -1-yl)-3,5-dichlorobenzoic acid 598.1 (MH)- P-0133

4-(3-(3-(benzyloxy)benzyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b] (Pyridin-1-yl)-3,5-dichlorobenzoic acid 612.0 (MH)- P-0134

4-(3-(Cyclobutylmethyl)-1-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethyl Isoxazole 389.6 P-0135

(S)-3-(Benzyloxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl) -1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methoxybenzoic acid 575.1 P-0136

3-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-phenylethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl) -2-Methoxybenzoic acid 468.6 P-0137

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-(oxetan-3-yloxy)benzoic acid 511.5 P-0138

(S)-3-(Cyclopropylmethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl Yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 509.6 P-0139

(S)-3-(Benzyloxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl) -1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 545.5 P-0140

3-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-phenylethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl) -4-Methoxybenzoic acid 468.6 P-0141

4-chloro-3-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-phenylethyl)-1H-pyrrolo[3,2-b]pyridine- 3-yl)benzoic acid 473.0 P-0142

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[3,2 -b)pyridin-3-yl)-3-methoxybenzoic acid 469.6 P-0143

5-(3-(Cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridine-2 -alcohol 375.2 P-0144

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-hydroxy-5-methoxybenzoic acid 485.6 P-0145

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)pyridin-2-ol 412.2 P-0146

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[3,2 -b)pyridin-3-yl)-3,5-dimethoxybenzoic acid 499.6 P-0147

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b]pyridin-3-yl)-3,5-diethoxybenzoic acid 527.6 P-0148

(S)-4-chloro-3-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)propyl)-1H-pyrrolo [3,2-b]pyridin-3-yl)benzoic acid 487.5 P-0149

3,5-Dichloro-4-(3-(cyclobutylmethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-c]pyridine- 1-yl)benzoic acid 471.0 P-0150

3,5-Dichloro-4-(6-(3,5-dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl) benzoic acid 478.0 P-0151

3,5-Dichloro-4-(3-(3,6-dihydro-2H-piperan-4-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H -Pyrrolo[3,2-b]pyridin-1-yl)benzoic acid 485.7 P-0152

(S)-3-(Cyclopropylmethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl Yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methoxybenzoic acid 539.6 P-0153

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-methoxy-5-(2,2,2-trifluoroethoxy)benzoic acid 566.5 P-0154

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid 507.1 P-0155

4-(3-(2-chlorophenyl)-1-(1,1-bis(pyridin-2-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)- 3,5-Dimethylisoxazole 506.1 P-0156

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-(Trifluoromethoxy)benzoic acid 512.1 P-0157

4-(1-((3,3-Difluorocyclobutyl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 522.5 P-0158

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 495.5 P-0159

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(pyridin-2-ylmethyl)-1H-pyrrolo[3,2-b]pyridin-1-yl )-3-(Trifluoromethoxy)benzoic acid 509.5 P-0160

(S)-3,5-Dimethyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2 -(Trifluoromethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)isoxazole 467.6 P-0161

(S)-2-(3-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoro (Methyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)phenyl)acetic acid 521.6 P-0162

(S)-3-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid 507.5 P-0163

4-(3-(Dicyclopropyl(hydroxy)methyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1 -Yl)-3-(trifluoromethoxy)benzoic acid 528.1 P-0164

4-chloro-3-(1-(1,1-bis(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[ 3,2-b)pyridin-3-yl)benzoic acid 550.1 P-0165

4-(3-(Dicyclopropyl(hydroxy)methyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1 -Yl)-3,5-diethoxy benzoic acid 532.2 P-0166

4-cyano-3-(1-(1,1-bis(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo [3,2-b]pyridin-3-yl)benzoic acid 541.1 P-0167

4-(1-(1,1-bis(pyridin-2-yl)ethyl)-3-(2-ethynylphenyl)-1H-pyrrolo[3,2-b]pyridin-6-yl) -3,5-Dimethylisoxazole 496.6 P-0168

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethyl Oxybenzoic acid 498.6 P-0169

2-(1-(1,1-bis(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2- b)Pyridin-3-yl)benzonitrile 497.1 P-0170

(S)-3-Cyclopropoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 495.6 P-0171

(S)-3-(Cyclopropylethynyl)-4-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl )-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid 503.6 P-0172

3-(1-(1,1-bis(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2- b)Pyridin-3-yl)-4-methoxybenzoic acid 546.6 P-0173

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)- 3,5-diethoxy benzoic acid 499.1 P-0174

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-ethoxy-5-isopropoxybenzoic acid    P-0175

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 495.0 P-0176

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(4-methoxypyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 525.0 P-0177

4-(1-(4-chloropyridin-3-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 529.0 P-0178

(S)-3-(Cyclopropylethynyl)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl )-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 503.2 P-0179

(S)-3-Cyclobutoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 509.1 P-0180

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-(trifluoromethyl)pyridin-2-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 563.1 P-0181

(S)-3-cyclopropyl-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H- Pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 479.1 P-0182

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-fluoropyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 513.1 P-0183

4-(1-(3-chloropyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 529.5 P-0184

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(4-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-1-yl)- 3,5-diethoxy benzoic acid 516.1 P-0185

4-(3-(3-chlorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)- 3,5-diethoxy benzoic acid 532.1 P-0186

4-(3-(2,4-Difluorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Yl)-3,5-diethoxybenzoic acid 534.1 P-0187

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(pyridin-2-ylmethyl)-1H-pyrrolo[3,2-b]pyridin-1-yl )-3,5-diethoxybenzoic acid 513.2 P-0188

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethyl (Oxy)benzoic acid 494.1 P-0189

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(4-methylpyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 509.5 P-0190

4-(3-(cyclobutylmethyl)-6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-1H-pyrrolo[3,2-b]pyridine -1-yl)-3,5-diethoxybenzoic acid 490.1 P-0191

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(2-(N-morpholinyl)ethyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 531.5 P-0192

4-(3-(6-Cyclopropylpyridin-3-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine- 1-yl)-3,5-diethoxybenzoic acid 539.6 P-0193

4-(3-(5-chloropyridin-3-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Yl)-3,5-diethoxybenzoic acid 533.1 P-0194

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(2-fluoro-4-methoxyphenyl)-1H-pyrrolo[3,2-b]pyridine -1-yl)-3,5-diethoxybenzoic acid    P-0195

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-b ]Pyridin-1-yl)-3,5-diethoxybenzoic acid 502.6 P-0196

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-3-(trifluoromethyl (Oxy)benzoic acid 494.0 P-0197

(S)-3,5-Dichloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 507.1 P-0198

3-chloro-4-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-5-(trifluoromethoxy)benzoic acid 546.1 P-0199

4-(1-(2-cyano-1-cyclopropylethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 511.1 P-0200

4-(1-(2-cyano-1-cyclopentylethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b] Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 539.1 P-0201

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(2-methoxypyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridine- 1-yl)-3,5-diethoxybenzoic acid 530.2 P-0202

4-(1-(Cyclopropylsulfonyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-(Trifluoromethoxy)benzoic acid 522.0 P-0203

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(2-isopropylpyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 537.5 P-0204

4-(1-(4-cyanopyridin-3-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 520.1 P-0205

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-3-ethoxy- 5-fluorobenzoic acid 472.1 P-0206

2-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-3-ethoxybenzene Formonitrile 435.1 P-0207

3-chloro-2-(6-(3,5-dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)benzonitrile 425.0 P-0208

4-(3-(4,4-Difluorocyclohex-1-en-1-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3, 2-b)pyridin-1-yl)-3,5-diethoxybenzoic acid 538.6 P-0209

4-(3-(3-chloro-4-fluorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1 -Yl)-3,5-diethoxybenzoic acid 550.1 P-0210

4-(3-(Cyclobutylmethyl)-6-(3-(methoxymethyl)-5-methylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine- 1-yl)-3,5-diethoxybenzoic acid 520.1 P-0211

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-methylpyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 509.1 P-0212

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1,1-dioxyltetrahydro-2H-thiopiperan-4-yl)-1H-pyrrole And [2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 550.1 P-0213

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-isopropoxybenzoic acid 486.2 P-0214

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-(2,2,2-trifluoroethoxy)benzoic acid 526.1 P-0215

4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 520.1 P-0216

4-(1-(3-(Cyclopropylethynyl)pyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 559.1 P-0217

4-(3-(4-cyano-2-fluorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine- 1-yl)-3,5-diethoxybenzoic acid 541.2 P-0218

4-(3-(4-(cyclopropylaminocarboxyl)phenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b ]Pyridin-1-yl)-3,5-diethoxybenzoic acid 581.2 P-0219

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-dimethyl Methyl oxybenzoate 484.1 P-0220

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-dimethyl Oxybenzoic acid 470.1 P-0221

4-(1-(2,6-Dimethoxyphenyl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxazole 426.6 P-0222

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Yl)-3,5-diethoxybenzoic acid 517.1 P-0223

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 512.1 P-0224

4-(1-(2-Chloro-6-ethoxyphenyl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxan Azole 444.0 P-0225

3-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-4-ethoxybenzene Formic acid 454.1 P-0226

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 502.1 P-0227

4-(1-(4,4-Difluorocyclohexyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 536.1 P-0228

4-(5-(3,5-Dimethylisoxazol-4-yl)-2-methyl-1-(pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 509.1 P-0229

4-(3-(2,4-Difluorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Yl)-3-(trifluoromethoxy)benzoic acid 530.1 P-0230

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-fluoro-5-(trifluoromethoxy)benzoic acid 530.1 P-0231

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(o-tolyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3- (Trifluoromethoxy)benzoic acid 508.1 P-0232

4-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 530.1 P-0233

4-(1-(2,5-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 530.0 P-0234

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-3-fluorobenzoic acid 525.4 P-0235

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-3-methylbenzoic acid 521.2 P-0236

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-3-methoxybenzoic acid 537.4 P-0237

(S)-4-(3-(3-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-( Trifluoromethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-3,5-dimethylisoxazole 507.1 P-0238

(S)-3-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-4-fluorobenzoic acid 525.4 P-0239

(S)-3-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-4-methoxybenzoic acid 537.4 P-0240

(S)-3-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-5-fluorobenzoic acid 525.4 P-0241

(S)-3-Chloro-5-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(three (Fluoromethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid 541.3 P-0242

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-2-fluorobenzoic acid 521.2 P-0243

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-2-methylbenzoic acid 521.2 P-0244

(S)-4-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-2-methoxybenzoic acid 537.4 P-0245

(S)-3-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-2-fluorobenzoic acid 525.4 P-0246

(S)-3-(6-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(trifluoromethyl) -1H-pyrrolo[3,2-b]pyridin-3-yl)-2-methylbenzoic acid 521.2 P-0247

(S)-2-Chloro-3-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(three (Fluoromethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid 541.3 P-0248

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4-ethoxy-2-hydroxybenzoic acid methyl ester 534.2 P-0249

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4-ethoxy-2-hydroxybenzoic acid 506.1 P-0250

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4-ethoxy-2-methoxybenzoic acid 520.1 P-0251

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(4-fluoropyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 513.1 P-0252

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(4-hydroxypyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 511.1 P-0253

4-(1-(3-chloropyridin-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 529.0 P-0254

4-(1-(2-cyano-6-fluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 537.1 P-0255

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methoxy- 5-methylbenzoic acid 454.1 P-0256

(S)-3-cyano-4-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-( Trifluoromethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid 532.3 P-0257

(S)-4-chloro-3-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-2-(three (Fluoromethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid 541.3 P-0258

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(1-((methylsulfonyl)methyl)-1H-pyrazol-4-yl)-1H -Pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid 580.3 P-0259

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrrolo [3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid 544.3 P-0260

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)- 1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid 560.2 P-0261

4-(3-(1-(Difluoromethyl)-1H-pyrazol-4-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3 ,2-b)pyridin-1-yl)-3,5-diethoxybenzoic acid 538.6 P-0262

4-(3-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)-6-(3,5-dimethylisoxazol-4-yl) -1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid 559.3 P-0263

4-(3-(1,3-dimethyl-1H-pyrazol-4-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3, 2-b)pyridin-1-yl)-3,5-diethoxybenzoic acid 516.4 P-0264

4-(3-(1-(Cyclopropylmethyl)-1H-pyrazol-4-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[ 3,2-b)pyridin-1-yl)-3,5-diethoxybenzoic acid 542.5 P-0265

4-(3-(1-Cyclopropyl-1H-pyrazol-4-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2- b)Pyridin-1-yl)-3,5-diethoxybenzoic acid 528.4 P-0266

4-(3-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo [3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid 541.3 P-0267

4-(3-(1-(2-(dimethylamino)-2-oxoethyl)-1H-pyrazol-4-yl)-6-(3,5-dimethylisoxan (Azol-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-diethoxybenzoic acid 573.4 P-0268

3-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4-(trifluoromethoxy)benzoic acid 530.1 P-0269

4-(3-(2,4-Difluorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Group) -3,5-diisopropoxybenzoic acid 562.1 P-0270

4-(3-(cyclobutylmethyl)-6-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)-1H-pyrrolo[3,2-b]pyridine -1-yl)-3,5-diethoxybenzoic acid 490.1 P-0271

4-(3-(4,4-Difluorocyclohexyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Yl)-3,5-diethoxybenzoic acid 540.1 P-0272

2-(4-(1-(3-(Cyclopropylethynyl)pyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)-1H-pyrazol-1-yl)acetic acid 479.2 P-0273

3-(Difluoromethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b]pyridine-3 -Based) benzoic acid 476.1 P-0274

3-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-4-(trifluoromethyl (Oxy)benzoic acid 494.0 P-0275

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b]pyridin-3-yl)-3-isopropoxy benzoic acid 468.1 P-0276

3-cyclobutoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b]pyridin-3-yl) benzoic acid 480.1 P-0277

3-(2,2-Difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b ]Pyridin-3-yl)benzoic acid 490.1 P-0278

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(2,2 ,2-Trifluoroethoxy)benzoic acid 508.1 P-0279

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 512.0 P-0280

2-(4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-1H-pyrazol-1-yl)acetic acid 432.2 P-0281

4-(1-(2-(azetidin-1-yl)pyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 551.1 P-0282

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(4-(methylsulfonyl)phenyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 572.0 P-0283

3-chloro-4-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-5-isopropoxybenzoic acid 520.2 P-0284

3-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -4-(trifluoromethoxy)benzoic acid 512.1 P-0285

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 488.1 P-0286

(R)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 488.1 P-0287

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[ 2,3-b)pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 526.1 P-0288

4-(1-(1-(Difluoromethyl)-3-methyl-1H-pyrazol-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 548.1 P-0289

4-(1-(1-(Difluoromethyl)-5-methyl-1H-pyrazol-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 548.1 P-0290

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-(Trifluoromethoxy)benzoic acid 501.1 P-0291

4-(1-(1-Acetylpiperidin-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 543.1 P-0292

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 579.1 P-0293

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(3-fluoropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid 513.1 P-0294

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)- 1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 556.1 P-0295

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4-ethoxypicolinic acid 491.1 P-0296

4-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3,5-diethoxy-2,6-difluorobenzoic acid 570.1 P-0297

4-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3,5-diethoxy-2-fluorobenzoic acid 552.1 P-0298

4-(6-(3,5-Dimethylisoxazol-4-yl)-3-phenyl 1H-pyrrolo[3,2-b]pyridin-1-yl)-3,5-bis( 2,2,2-Trifluoroethoxy)benzoic acid 606.1 P-0299

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)- 1H-pyrrolo[2,3-b]pyridin-3-yl)-3-isopropoxybenzoic acid 530.2 P-0300

4-(1-(2-(azetidin-1-yl)pyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)-3-isopropoxybenzoic acid 525.1 P-0301

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-isopropoxybenzoic acid 462.1 P-0302

4-(3-(2-isopropoxy-4-(methylsulfonyl)phenyl)-1-phenyl 1H-pyrrolo[2,3-b]pyridin-5-yl)-3, 5-Dimethylisoxazole 502.1 P-0303

4-amino-5-(1-(2,4-difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-1-propyl-1H-pyrazole-3-carboxylic acid 493.1 P-0304

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4-(ethylamino)-1-propyl-1H-pyrazole-3-carboxylic acid 521.2 P-0305

(E)-4-(1-(4-Cyclopropylbut-3-en-1-yl)-5-(1,4-dimethyl-1H-1,2,3-triazole-5- Yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 512.1 P-0306

4-(1-(3-chloropyridin-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(2,2-difluoroethoxy)benzoic acid 525.1 P-0307

4-(1-(2-chlorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 528.1 P-0308

4-(1-(2-Cyclopropylphenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl )-3-(Trifluoromethoxy)benzoic acid 534.1 P-0309

4-(1-(2-cyanophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-(Trifluoromethoxy)benzoic acid 519.4 P-0310

4-(1-(4-cyano-2-methylphenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 533.2 P-0311

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(2-fluoro-4-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 542.2 P-0312

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(2-(prop-1-en-2-yl)phenyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 534.1 P-0313

4-(1-(4-cyanophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-(Trifluoromethoxy)benzoic acid 519.1 P-0314

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(4-(2-hydroxyprop-2-yl)phenyl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 552.4 P-0315

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(thiophen-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 500.2 P-0316

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(2-methoxypyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 525.4 P-0317

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(2-methylpyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 509.2 P-0318

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 498.4 P-0319

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(pyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 496.3 P-0320

4-(1-(2-Aminopyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 511.3 P-0321

4-(1-(2-(Dimethylamino)pyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 539.5 P-0322

4-(1-(4-carboxyphenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 3-(Trifluoromethoxy)benzoic acid 538.3 P-0323

4-(1-(4-aminocarboxylphenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-3-(trifluoromethoxy)benzoic acid    P-0324

5-(1-(3-chloropyridin-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4-methoxypicolinic acid 476.0 P-0325

(S)-3-(2,2-Difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)- 1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 484.0 P-0326

3-(2,2-Difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-ethyl-3-methyl-1H -Pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 522.1 P-0327

3-(2,2-Difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2,3-b ]Pyridin-3-yl)-5-fluorobenzoic acid 508.1 P-0328

4-(1-(2-(azetidin-1-yl)pyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)-3-(2,2-difluoroethoxy)benzoic acid 547.2 P-0329

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4,6-diethoxypicolinic acid 535.2 P-0330

4-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-5-ethoxy-2-fluorobenzoic acid 508.1 P-0331

4-(1-(2-(azetidin-1-yl)pyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)-3-chloro-5-(2,2-difluoroethoxy)benzoic acid 581.1 P-0332

3-chloro-5-(2,2-difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-phenyl 1H-pyrrolo[2 ,3-b)pyridin-3-yl)benzoic acid 524.0 P-0333

(S)-3-Chloro-5-(2,2-difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3 -Yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 518.1 P-0334

4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-cyclobutoxybenzoic acid 506.2 P-0335

4-(1-(1-(cyanomethyl)cyclobutyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 511.0 P-0336

4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-isopropoxybenzoic acid 494.0 P-0337

4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-cyclopropoxybenzoic acid 492.0 P-0338

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-(2,2-difluoroethoxy)benzoic acid 508.2 P-0339

5-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -4-Methoxypicolinic acid 459.2 P-0340

3-chloro-4-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-5-(2,2-difluoroethoxy)benzoic acid 542.1 P-0341

3-cyclobutoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[ 2,3-b)pyridin-3-yl)benzoic acid 488.2 P-0342

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-isopropoxybenzoic acid 500.2 P-0343

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 526.1 P-0344

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-indol-3-yl)-3-(trifluoromethoxy Base) benzoic acid 511.1 P-0345

4-(1-(3-Cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-2-methyl-1H-pyrrolo[2,3- b)Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 534.0 P-0346

(S)-3-Chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-5-(trifluoromethoxy)benzoic acid 522.1 P-0347

4-(1-(2-(azetidin-1-yl)pyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)-3-cyclobutoxybenzoic acid 537.1 P-0348

4-(1-(2-(azetidin-1-yl)pyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)-3-(2,2-difluoroethoxy)-5-fluorobenzoic acid 565.1 P-0349

3-(2,2-Difluoroethoxy)-4-(1-(1-(Difluoromethyl)-3-methyl-1H-pyrazol-4-yl)-5-(3,5 -Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 544.0 P-0350

(S)-3-cyclobutoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)benzoic acid 474.2 P-0351

3-cyclobutoxy-4-(1-(1-(difluoromethyl)-3-methyl-1H-pyrazol-4-yl)-5-(3,5-dimethylisoxazole) -4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 534.1 P-0352

3-chloro-5-(2,2-difluoroethoxy)-4-(1-(1-(difluoromethyl)-5-methyl-1H-pyrazol-4-yl)-5- (3,5-Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 578.0 P-0353

3-cyclobutoxy-4-(1-(1-(difluoromethyl)-5-methyl-1H-pyrazol-4-yl)-5-(3,5-dimethylisoxazole) -4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 534.1 P-0354

4-(1-(1-(Difluoromethyl)-5-methyl-1H-pyrazol-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)-3-isopropoxybenzoic acid 520.0 P-0355

3-chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-5-(trifluoromethoxy)benzoic acid 536.1 P-0356

3-chloro-5-cyclobutoxy-4-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)benzoic acid 532.2 P-0357

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-isopropoxybenzoic acid 476.2 P-0358

3-chloro-5-cyclobutoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 522.1 P-0359

3-chloro-5-(2,2-difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan -4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 532.0 P-0360

(S)-4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-5-ethoxy-2-fluorobenzoic acid 466.1 P-0361

(S)-3-chloro-5-cyclobutoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrole And [2,3-b]pyridin-3-yl)benzoic acid 508.1 P-0362

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-4-methoxypicolinic acid 449.2 P-0363

3-chloro-5-cyclopropoxy-4-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2 ,3-b)pyridin-3-yl)benzoic acid 518.1 P-0364

4-(1-((1-cyanocyclobutyl)methyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-(trifluoromethoxy)benzoic acid 511.2 P-0365

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(2-hydroxy-2-methylpropyl)-3-methyl-1H-pyrazole- 4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 570.2 P-0366

4-(1-(1-(2-(Dimethylamino)-2-oxoethyl)-3-methyl-1H-pyrazol-4-yl)-5-(3,5- Dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 583.2 P-0367

3-(2,2-Difluoroethoxy)-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl) )-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylbenzoic acid 512.1 P-0368

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-6-methoxypicolinic acid 449.2 P-0369

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-fluoro-5-isopropoxybenzoic acid 504.2 P-0370

3-chloro-4-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-5-ethoxybenzoic acid 506.2 P-0371

3-chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3 -b]pyridin-3-yl)-5-ethoxybenzoic acid 496.2 P-0372

3-chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3 -b]pyridin-3-yl)-5-isopropoxybenzoic acid 510.2 P-0373

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-4,6-diethoxypicolinic acid 507.2 P-0374

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3,5-diethoxy-2-fluorobenzoic acid 524.2 P-0375

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-5-ethoxy-2-fluorobenzoic acid 480.2 P-0376

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-6-ethoxypicolinic acid 463.2 P-0377

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 5-ethoxy-2-fluorobenzoic acid 490.1 P-0378

4-(1-Cyclobutyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(three (Fluoromethoxy)benzoic acid 472.1 P-0379

3-cyclopropoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[ 2,3-b)pyridin-3-yl)benzoic acid 474.5 P-0380

3-chloro-4-(1-(dicyclobutylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-5-(trifluoromethoxy)benzoic acid 574.1 P-0381

3-chloro-5-cyclopropoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 508.1 P-0382

4-(1-Cyclopentyl-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(three (Fluoromethoxy)benzoic acid 486.1 P-0383

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(3-methyltetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-(trifluoromethoxy)benzoic acid 502.0 P-0384

4-(1-(2-Cyclopropylpyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 536.1 P-0385

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(4-methyltetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 516.0 P-0386

3-chloro-4-(1-(2-cyclopropylpyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-5-(trifluoromethoxy)benzoic acid 570.1 P-0387

4-(1-(2-Cyclopropylpyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(2,2-difluoroethoxy)benzoic acid 532.2 P-0388

4-(1-(6-Cyclopropylpyridin-3-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 535.2 P-0389

4-(1-(3-cyanocyclopentyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl )-3-(Trifluoromethoxy)benzoic acid 511.1 P-0390

3-chloro-4-(1-(2-cyclopropylpyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-5-(2,2-difluoroethoxy)benzoic acid 566.1 P-0391

3-chloro-5-cyclobutoxy-4-(1-(2-cyclopropylpyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H- Pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 556.1 P-0392

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(2-methoxypyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-3-(trifluoromethoxy)benzoic acid 526.1 P-0393

3-chloro-4-(1-(2-cyclopropylpyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-5-isopropoxybenzoic acid 544.1 P-0394

3-cyclopropoxy-4-(1-(dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-5-fluorobenzoic acid 502.2 P-0395

3-chloro-4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-5-(trifluoromethoxy)benzoic acid 554.1 P-0396

3-chloro-4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-5-cyclobutoxybenzoic acid 540.0 P-0397

3-cyclopropoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[ 2,3-b)pyridin-3-yl)-5-fluorobenzoic acid 492.2 P-0398

3-chloro-5-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3 -b]pyridin-3-yl)-6-ethoxypicolinic acid 497.1 P-0399

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-methyl-6-pendant oxy-1,6-dihydropyridin-3-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 525.1 P-0400

4-(5-(3-ethyl-5-methylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 516.1 P-0401

4-(5-(5-ethyl-3-methylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-3-(trifluoromethoxy)benzoic acid 516.1 P-0402

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-isopropoxy-5-methylbenzoic acid 490.1 P-0403

4-(5-(3,5-Dimethylisoxazol-4-yl)-1-(4-methyltetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-3-isopropoxybenzoic acid 490.2 P-0404

3-chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(4-methyltetrahydro-2H-piperan-4-yl)-1H-pyrrolo [2,3-b]pyridin-3-yl)-5-isopropoxybenzoic acid 524.2 P-0405

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(4-methyltetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3 -b]pyridin-3-yl)-6-ethoxypicolinic acid 477.1 P-0406

(S)-3-Chloro-5-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-6-ethoxypicolinic acid 483.1 P-0407

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(3-methyltetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-3-isopropoxybenzoic acid 476.1 P-0408

3-chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(3-methyltetrahydrofuran-3-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-5-isopropoxybenzoic acid 510.1 P-0409

3-chloro-4-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b ]Pyridin-3-yl)-5-cyclopropoxybenzoic acid 526.1 P-0410

3-cyclobutoxy-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[ 2,3-b)pyridin-3-yl)-5-fluorobenzoic acid 506.2 P-0411

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-6-ethoxy-4-methylpicolinic acid 477.2 P-0412

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-6-ethoxy-4-methylpicolinic acid 505.2 P-0413

3-cyclopropoxy-4-(5-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-1-(tetrahydro-2H-piperan-4- Yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid Insert P-0414

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 4,6-diethoxypicolinic acid 517.2 P-0415

(S)-5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-4,6-diethoxypicolinic acid 528.2 P-0416

5-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -6-Ethoxy-3-methylpicolinic acid 487.2 P-0417

5-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -6-Ethoxy-4-methylpicolinic acid 487.2 P-0418

4-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -3-methylpicolinic acid 443.2 P-0419

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-methylpicolinic acid 433.2 P-0420

5-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -4,6-diethoxypicolinic acid 517.2 P-0421

5-(1-(3-cyanopyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3 -Yl)-4,6-diethoxypicolinic acid 525.1 P-0422

5-(1-(3-aminomethylpyridin-2-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-4,6-diethoxypicolinic acid 543.2 P-0423

5-(1-(4-cyano-2-fluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-4,6-diethoxypicolinic acid 542.2 P-0424

5-(1-(2-Cyclopropylpyrimidin-5-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-4,6-diethoxypicolinic acid 541.2 P-0425

5-(1-(4,4-Difluorocyclohexyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4,6-diethoxypicolinic acid 541.2 P-0426

5-(1-(6-Cyclopropylpyridin-3-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-4,6-diethoxypicolinic acid 540.2 P-0427

5-(1-(Dicyclopropylmethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl) -4-ethoxypicolinic acid 473.2 P-0428

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(tetrahydro-2H-piperan-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-4-ethoxypicolinic acid 463.2 P-0429

5-(1-(1-(Difluoromethyl)-3-methyl-1H-pyrazol-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H -Pyrrolo[2,3-b]pyridin-3-yl)-4,6-diethoxypicolinic acid 553.2 P-0430

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[ 2,3-b)pyridin-3-yl)-4,6-diethoxypicolinic acid 531.2 P-0431

5-(3-(2,4-Difluorophenyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridine-1- Yl)-4,6-diethoxypicolinic acid 535.2 P-0432

5-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Yl)-4,6-diethoxypicolinic acid methyl ester 549.2 P-0433

5-(1-(1-(Third-butoxycarbonyl)piperidin-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)-4,6-diethoxypicolinic acid 606.3 P-0434

4-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3- Base) cyclohexane-1-carboxylic acid 452.2 P-0435

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrrolo[2,3 -b)pyridin-3-yl)-4,6-diethoxypicolinic acid 584.2 P-0436

5-(5-(3,5-Dimethylisoxazol-4-yl)-1-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)- 4,6-diethoxypicolinic acid 500.0 P-0437

2-(4-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-3-fluorophenyl)acetic acid 478.1 P-0438

2-(4-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)phenyl)acetic acid 460.1 P-0439

3-chloro-4-(5-(3,5-dimethylisoxazol-4-yl)-1-(pyridazin-3-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-5-(trifluoromethoxy)benzoic acid 530.1 P-0440

3-chloro-4-(1-(6-cyclopropylpyridin-3-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-5-(trifluoromethoxy)methyl benzoate 583.1 P-0441

3-chloro-4-(1-(6-cyclopropylpyridin-3-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3- b)Pyridin-3-yl)-5-(trifluoromethoxy)benzoic acid 569.1 P-0442

4-(1-(1-(Third-butoxycarbonyl)piperidin-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)-5-ethoxy-2-fluorobenzoic acid 579.3 P-0443

2-(3-(1-(2,4-Difluorophenyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine -3-yl)-4-methoxyphenyl)acetic acid 490.1 P-0444

4-(1-(6-Cyclopropylpyridin-3-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2,3-b]pyridine- 3-yl)-2-fluoro-5-(trifluoromethoxy)benzoic acid 553.2 P-0445

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-pentylpiperidin-4-yl)-1H-pyrrolo[2,3-b] (Pyridin-3-yl)-5-ethoxy-2-fluorobenzoic acid 563.3 P-0446

4-(1-(1-(2-cyanoethyl)piperidin-4-yl)-5-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)-5-ethoxy-2-fluorobenzoic acid 532.2 P-0447

4-(5-(3,5-dimethylisoxazol-4-yl)-1-(1-(2-hydroxyacetyl)piperidin-4-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)-5-ethoxy-2-fluorobenzoic acid 537.2 P-0448

3-chloro-4-(1-(6-cyclopropylpyridin-3-yl)-5-(5-ethyl-3-methylisoxazol-4-yl)-1H-pyrrolo[2, 3-b)pyridin-3-yl)-5-(trifluoromethoxy)benzoic acid 583.2 P-0449

(S)-3-(5-(1,4-Dimethyl-1H-1,2,3-triazol-5-yl)-1-(1-(pyridin-2-yl)ethyl)- 1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid 439.1 Biological examples Biological test method The following analytical methods were used to test the compounds of the present invention: EP300 Alphascreen Combined analysis

The Alphascreen™ binding assay was used to evaluate the binding of the compound of formula (I) to EP300. Recombinant EP300 protein (an acetylated histone 3 peptide) and AlphaScreen™ technology are used to quantitatively measure the inhibition of interaction between the bromodomain of EP300 and its acetylated target protein. In the absence of inhibition of EP300 protein binding to AlphaScreen™, nickel chelator receptor beads can interact with acetylated histone 3 peptides immobilized by AlphaScreen™ streptavidin-coated beads . This interaction brings the donor and acceptor beads close together. The close proximity allows the singlet oxygen generated by the laser excitation of the donor beads to reach the acceptor beads and generate a luminescent signal. EP300 inhibitors are used to reduce the proximity signal by inhibiting the EP300-acetylated peptide interaction.

Prepare and purify recombinant human EP300 (EP300-BD (1040-1161)) containing bromo domain as described in the protein expression and purification section. The peptide is human histone H3 _45-64 K56 _Ac -Biotin (Anaspec CA, USA).

Protocol for EP300 analysis: prepare all components in a buffer consisting of 50 mM HEPES pH 7.5, 50 mM NaCl, 0.01% BSA, 0.01% Triton X-100, 2 mM DTT. Dilute the test compound and DMSO vehicle 1:50 in buffer and transfer a volume of 4 µL to Alphaplate. In Alphaplate (PerkinElmer GA, USA), 5.5 µL of EP300 protein and 5.5 µL of peptide were added to wells containing 4 µL of various concentrations of the test compound of formula (I) or DMSO vehicle and incubated at room temperature for 1 hour. Then add 5 µL of the donor and acceptor bead mixture at a final concentration of 7.5 µg/ml. 60 minutes after the beads were added, the Alpha signal (λ _Ex 680 nm, λ _Em 520-620 nm) was read with an Envision spectrometer. The final concentrations of bromodomain proteins and peptides are shown below. Analysis method name EP300 protein (nM) Peptide (nM) EP300-BD 50 150

All data were normalized to the average of 16 high and 16 low control wells on each plate. Then apply the following four-parameter curve fitting: Y=A+((BA)/(1+((C/x)^D))) Among them, "A" is the minimum value, "B" is the maximum value, "C" is IC50 and "D" is Hill slope. Protein expression and purification

Use N-terminal hexa-His tag to express recombinant human EP300 bromodomain (EP300-BD (1040-1161)) in E. coli cells (in the modified pET vector) and use IMAC (Ni-affinity) ) And a combination of size exclusion chromatography steps for purification.

E. coli strain BL21-CodonPlus (DE3) (Agilent Technologies CA, USA) was used to express recombinant EP300 protein. Cells were grown in Terrific Broth (TB) medium at 37°C to an OD600 of 0.7, then the temperature was lowered to 18°C and induced with 1.0 mM isopropyl-β-D-thiogalactoside ("IPTG") The protein was collected for 20 hours by centrifugation at 8500×g for 20 minutes. _{Resuspend the cells in 0.1 MK 2} PO ₄ pH 8.0, 250 mM NaCl, 10% together with 0.2 mg/ml lysozyme, 0.2 mM phenylmethanesulfonate fluoride ("PMSF"), and 25 µg/ml DNase I In glycerol, 0.75% NP-40, 25 mM imidazole, incubate on ice for 30 minutes and dissolve with a cell disintegrant (MicroFluidics MA, USA). The lysate was clarified by centrifugation at 20,000×g for 1 hour. The protein was captured with Ni-NTA resin (Life Technologies, USA). Wash contaminated proteins with 50 mM HEPES pH 7.5, 500 mM NaCl, and 5% glycerol. After 3 washing steps, use 50 mM HEPES pH 7.5, 500 mM NaCl, and 5% glycerol containing 10, 25, 50, 100, 150 and 250 mM imidazole to gradually dissolve the protein. The protein was further purified using a size exclusion column (26/600 Superdex 200, GE Biosciences NJ, USA) in 10 mM HEPES pH 7.5,500. BRD4 Alphascreen combined analysis method

The Alphascreen binding analysis method was used to evaluate the binding of the compound of formula (I) to BRD4. Use recombinant BRD4 protein, acetylated histone 4 peptide and AlphaScreen™ technology to quantitatively measure the inhibition of interaction between BRD4 and its acetylated target protein. In the absence of inhibition of BRD4 protein bound to AlphaScreen™, nickel chelator receptor beads can interact with acetylated histone 4 peptides immobilized by AlphaScreen™ streptavidin-coated beads . This interaction brings the donor and acceptor beads close together. The close proximity allows the singlet oxygen generated by the laser excitation of the donor beads to reach the acceptor beads and generate a luminescent signal. BRD4 inhibitors are used to reduce the proximity signal by inhibiting the interaction of BRD4-acetylated peptides.

Prepare and purify the recombinant human BRD4 (BRD4-BD12(1-477)) containing the double bromodomain as described in the protein expression and purification section. The peptide is human histone H4 _1-21 K5 _Ac K8 _Ac K12 _Ac K16 _Ac -Biotin (Anaspec CA, USA).

Protocol for BRD4 analysis: prepare all components in a buffer consisting of 50 mM HEPES pH 7.5, 50 mM NaCl, 0.01% BSA, 0.01% Triton X-100, 2 mM DTT. Dilute the test compound and DMSO vehicle 1:50 in buffer and transfer a volume of 4 µL to Alphaplate. In Alphaplate (PerkinElmer GA, USA), add 5.5 µL bromodomain protein and 5.5 µL peptide to wells containing 4 µL of various concentrations of the test compound of formula (I) or DMSO vehicle and incubate at room temperature for 1 hour . Then add 5 µL of the donor and acceptor bead mixture at a final concentration of 7.5 µg/ml. Thirty minutes after the beads were added, the Alpha signal (λ _Ex 680 nm, λ _Em 520-620 nm) was read with an Envision spectrometer. The final concentrations of bromodomain proteins and peptides are shown below. Analysis method name BRD protein (nM) Peptide (nM) BRD4-BD12 3.6 36

All data were normalized to the average of 16 high and 16 low control wells on each plate. Then apply the following four-parameter curve fitting: Y=A+((BA)/(1+((C/x)^D))) Among them, "A" is the minimum value, "B" is the maximum value, "C" is IC50 and "D" is Hill slope. Protein expression and purification

Use N-terminal hexa-His tag to express recombinant human BRD4 (BRD4-BD12(1-477)) containing dual bromodomain in E. coli cells (in the modified pET vector) and use IMAC (Ni-affinity) and A combination of size exclusion chromatography steps for purification.

E. coli strain BL21-CodonPlus (DE3) (Agilent Technologies CA, USA) was used to express recombinant BRD4. Cells were grown in Terrific Broth (TB) medium at 37°C to an OD600 of 2.0, then the temperature was lowered to 18°C, and induced with 0.1 mM isopropyl-β-D-thiogalactoside ("IPTG") The protein was collected for 12-18 hours by centrifugation at 8000×g for 20 minutes. Resuspend the cells in 40 mM Tris-HCl pH 8.0, 0.5 M NaCl, 25 mM imidazole, 5% glycerol, 1/200 volume Protease Inhibitor Cocktail Set III (Calbiochem), 5 mM β-mercaptoethanol ("BME") , 0.5 mg/mL lysozyme and 0.5 mg/mL DNaseI, incubate on ice for 30 minutes and dissolve with cell disintegrant (MicroFluidics MA, USA). The lysate was clarified by centrifugation at 20,000×g for 2 hours. The protein was captured with Ni-NTA resin (Life Technologies, USA). Wash contaminated proteins with 40 mM Tris-HCl pH 8.0, 0.5 M NaCl, 25 mM imidazole, 5% glycerol, and 5 mM BME. After 3 washing steps, the protein was gradually dissolved into washing buffer containing 50, 100, 150, 500 mM imidazole. The protein was further purified using Gel Filtration column 16/60 Superdex 200 (GE Biosciences NJ, USA) in 10 mM HEPES pH 8.0, 150 mM NaCl and 5 mM DTT. Glycerol was added to reach a final concentration of 12%, and the protein was aliquoted and flash frozen in liquid nitrogen. CBP Alphascreen combined analysis method

The Alphascreen™ binding assay was used to evaluate the binding of the compound of formula (I) to CBP. Use recombinant CBP (an acetylated histone 3 peptide) and AlphaScreen™ technology to quantitatively measure the inhibition of interaction between the CBP bromine domain and its acetylated target protein. In the absence of inhibition of CBP protein binding to AlphaScreen™, nickel chelator receptor beads can interact with acetylated histone 3 peptides immobilized by AlphaScreen™ streptavidin-coated beads . This interaction brings the donor and acceptor beads close together. The close proximity allows the singlet oxygen generated by the laser excitation of the donor beads to reach the acceptor beads and generate a luminescent signal. CBP inhibitors are used to cause a decrease in the proximity signal by inhibiting the CBP-acetylated peptide interaction.

Prepare and purify recombinant human CBP (CBP-BD (1043-1159)) containing bromo domain as described in the protein expression and purification section. The peptide is human histone H345-64K56Ac-Biotin (Anaspec CA, USA).

The protocol for CBP analysis: prepare all components in a buffer consisting of 50 mM HEPES pH 7.5, 50 mM NaCl, 0.01% BSA, 0.01% Triton X-100, 2 mM DTT. Dilute the test compound and DMSO vehicle 1:50 in buffer and transfer a volume of 4 µL to Alphaplate. In Alphaplate (PerkinElmer GA, USA), 5.5 µL of CBP protein and 5.5 µL of peptide were added to wells containing 4 µL of various concentrations of the test compound of formula (I) or DMSO vehicle and incubated at room temperature for 1 hour. Then add 5 µL of the donor and acceptor bead mixture at a final concentration of 7.5 µg/ml. 60 minutes after the beads were added, the Alpha signal (λEx 680 nm, λEm 520-620 nm) was read with an Envision spectrometer. The final concentrations of bromodomain proteins and peptides are shown below. Analysis method name CBP protein (nM) Peptide (nM) BD 50 150

All data were normalized to the average of 16 high and 16 low control wells on each plate. Then apply the following four-parameter curve fitting: Y=A+((BA)/(1+((C/x)^D))) Among them, "A" is the minimum value, "B" is the maximum value, "C" is IC50 and "D" is Hill slope. Protein expression and purification

Expression of recombinant human CBP bromodomain (CBP-BD (1043-1159)) in E. coli cells (in the modified pET vector) with N-terminal hexa-His tag and using IMAC (Ni-affinity) and size exclusion A combination of chromatographic steps performs purification.

E. coli strain BL21-CodonPlus (DE3) (Agilent Technologies CA, USA) was used to express the recombinant CBP protein. Cells were grown in Terrific Broth (TB) medium at 37°C to an OD600 of 0.92, then the temperature was lowered to 20°C and induced with 1.0 mM isopropyl-β-D-thiogalactoside ("IPTG") The protein was collected for 20 hours by centrifugation at 8500×g for 20 minutes. Resuspend the cells in 0.1 M K2PO4 together with 0.2 mg/ml lysozyme, 0.2 mM phenylmethanesulfonate fluoride ("PMSF"), 0.5β-mercaptoethanol ("BME"), and 25 µg/ml DNase I In pH 8.0, 250 mM NaCl, 10% glycerol, 0.75% NP-40, 25 mM imidazole, incubate on ice for 30 minutes and dissolve with cell disintegrant (MicroFluidics MA, USA). The lysate was clarified by centrifugation at 20,000×g for 1 hour. The protein was captured with Ni-NTA resin (Life Technologies, USA). Wash contaminated proteins with 40 mM HEPES pH 7.5, 500 mM NaCl, 5% glycerol, 5 mM imidazole, and 5 mM BME. After 3 washing steps, the protein was eluted with 40 mM HEPES pH 7.5, 400 mM NaCl, and 5 mM BME containing 400 mM imidazole. The protein was further purified using a size exclusion column (26/600 Superdex 200, GE Biosciences NJ, USA) in 40 mM HEPES pH 7.5, 250 mM NaCl, 5 mM BME. The protein was aliquoted and flash frozen in liquid nitrogen.

Table 2 below provides information indicating the biochemical and/or cytostatic activity of exemplary compounds as described in Table 1 herein. In Table 2 below, the activity is provided as follows: +++=0.0001 µM<IC ₅₀ ＜1 µM; ++=1 µM＜IC ₅₀ ＜8 µM, +=8 µM＜IC ₅₀ ＜1000 µM. Table 2 P# EP300 IC ₅₀ ( µ M ) BRD4 IC ₅₀ ( µ M ) CREBBP ( CBP ) IC ₅₀ ( µ M ) P-0001 +++ + +++ P-0002 +++ +++ +++ P-0003 + + + P-0004 +++ + +++ P-0005 + + + P-0006 ++ + ++ P-0007 +++ + +++ P-0008 +++ + +++ P-0009 +++ + +++ P-0010 +++ + +++ P-0011 +++ + ++ P-0012 +++ + +++ P-0013 +++ + +++ P-0014 +++ + +++ P-0015 +++ ++ +++ P-0016 +++ ++ +++ P-0017 +++ ++ +++ P-0018 +++ ++ +++ P-0019 ++ ++ ++ P-0020 ++ ++ ++ P-0021 ++ ++ ++ P-0022 + + + P-0023 ++ ++ ++ P-0024 ++ + ++ P-0025 +++ ++ +++ P-0026 +++ ++ +++ P-0027 +++ ++ +++ P-0028 +++ ++ +++ P-0029 +++ ++ +++ P-0030 ++ + ++ P-0031 +++ ++ +++ P-0032 +++ ++ +++ P-0033 +++ ++ +++ P-0034 +++ ++ +++ P-0035 +++ ++ +++ P-0036 +++ ++ +++ P-0037 ++ ++ ++ P-0038 +++ ++ +++ P-0040 +++ ++ +++ P-0041 +++ +++ +++ P-0042 +++ +++ +++ P-0043 +++ ++ +++ P-0044 +++ +++ +++ P-0045 +++ +++ +++ P-0046 +++ + +++ P-0047 +++ ++ +++ P-0048 +++ ++ +++ P-0049 +++ + +++ P-0050 +++ + +++ P-0051 +++ + +++ P-0052 +++ ++ +++ P-0053 +++ ++ +++ P-0054 +++ +++ +++ P-0055 +++ +++ +++ P-0056 +++ ++ +++ P-0057 +++ ++ +++ P-0058 +++ + +++ P-0059 +++ + +++ P-0060 +++ ++ +++ P-0061 +++ + +++ P-0062 +++ + +++ P-0063 +++ + +++ P-0064 +++ ++ +++ P-0065 +++ ++ +++ P-0066 +++ + +++ P-0067 +++ ++ +++ P-0068 +++ + +++ P-0069 +++ + +++ P-0070 +++ + +++ P-0071 +++ ++ +++ P-0072 +++ ++ +++ P-0073 +++ + +++ P-0074 +++ + +++ P-0075 +++ + +++ P-0076 ++ + ++ P-0077 +++ ++ +++ P-0078 +++ ++ ++ P-0079 +++ ++ +++ P-0080 ++ ++ ++ P-0081 +++ ++ ++ P-0082 ++ ++ + P-0083 +++ ++ ++ P-0084 +++ +++ +++ P-0085 +++ + ++ P-0086 +++ ++ +++ P-0087 +++ ++ +++ P-0088 +++ ++ +++ P-0089 +++ ++ +++ P-0090 +++ +++ +++ P-0091 +++ ++ +++ P-0092 +++ ++ ++ P-0093 +++ ++ +++ P-0094 +++ + +++ P-0095 +++ ++ +++ P-0096 +++ ++ ++ P-0097 +++ + +++ P-0098 +++ ++ +++ P-0099 +++ ++ +++ P-0100 +++ ++ +++ P-0101 +++ + +++ P-0102 ++ + ++ P-0103 +++ + +++ P-0104 +++ + +++ P-0105 +++ + +++ P-0106 ++ + ++ P-0107 ++ + ++ P-0108 +++ ++ +++ P-0109 +++ ++ +++ P-0110- +++ ++ +++ P-0111 +++ + +++ P-0112 +++ + +++ P-0113 +++ + +++ P-0114 +++ + +++ P-0115 +++ + +++ P-0116 +++ ++ +++ P-0117 +++ ++ +++ P-0118 +++ + +++ P-0119 +++ ++ +++ P-0120 +++ ++ ++ P-0121 +++ ++ +++ P-0122 ++ + ++ P-0123 +++ + +++ P-0124 +++ + +++ P-0125 +++ + +++ P-0126 +++ + +++ P-0127 +++ + +++ P-0128 +++ ++ +++ P-0129 +++ ++ +++ P-0130 + + + P-0131 +++ ++ +++ P-0132 +++ + +++ P-0133 +++ ++ +++ P-0134 ++ + ++ P-0135 +++ + +++ P-0136 +++ +++ +++ P-0137 +++ + +++ P-0138 +++ + +++ P-0139 +++ + +++ P-0140 +++ + ++ P-0141 +++ + +++ P-0142 +++ +++ +++ P-0143 ++ + ++ P-0144 +++ + +++ P-0145 ++ + + P-0146 ++ + ++ P-0147 +++ + +++ P-0148 +++ ++ +++ P-0149 +++ + +++ P-0150 +++ ++ +++ P-0151 +++ ++ +++ P-0152 +++ + +++ P-0153 +++ + +++ P-0154 +++ +++ +++ P-0155 +++ +++ +++ P-0156 +++ + +++ P-0157 +++ +++ +++ P-0158 +++ +++ +++ P-0159 +++ +++ +++ P-0160 +++ +++ +++ P-0161 +++ + +++ P-0162 +++ + +++ P-0163 +++ + +++ P-0164 +++ ++ +++ P-0165 +++ + +++ P-0166 +++ +++ +++ P-0167 +++ +++ +++ P-0168 +++ ++ +++ P-0169 +++ +++ +++ P-0170 +++ + +++ P-0171 +++ +++ +++ P-0172 ++ ++ ++ P-0173 +++ ++ +++ P-0174 +++ + +++ P-0175 +++ ++ +++ P-0176 +++ ++ +++ P-0177 +++ + +++ P-0178 ++ + ++ P-0179 +++ + +++ P-0180 +++ + +++ P-0181 +++ + +++ P-0182 +++ ++ +++ P-0183 +++ + +++ P-0184 +++ ++ +++ P-0185 +++ ++ +++ P-0186 +++ + +++ P-0187 +++ + +++ P-0188 +++ ++ +++ P-0189 +++ + +++ P-0190 +++ ++ +++ P-0191 +++ + +++ P-0192 +++ ++ +++ P-0193 +++ ++ +++ P-0194 +++ ++ +++ P-0195 +++ ++ +++ P-0196 +++ ++ +++ P-0197 +++ + +++ P-0198 +++ + +++ P-0199 +++ + +++ P-0200 +++ + +++ P-0201 +++ ++ +++ P-0202 +++ ++ +++ P-0203 +++ ++ +++ P-0204 +++ + +++ P-0205 +++ ++ +++ P-0206 +++ + +++ P-0207 ++ ++ ++ P-0208 +++ ++ +++ P-0209 +++ ++ +++ P-0210 +++ + +++ P-0211 +++ ++ +++ P-0212 +++ + +++ P-0213 +++ + +++ P-0214 +++ + +++ P-0215 +++ ++ +++ P-0216 +++ + +++ P-0217 +++ ++ +++ P-0218 +++ ++ +++ P-0219 +++ ++ +++ P-0220 +++ +++ +++ P-0221 +++ + ++ P-0222 +++ ++ +++ P-0223 +++ ++ +++ P-0224 ++ ++ ++ P-0225 +++ ++ +++ P-0226 +++ ++ +++ P-0227 +++ ++ +++ P-0228 +++ ++ +++ P-0229 +++ ++ +++ P-0230 +++ ++ +++ P-0231 +++ + +++ P-0232 +++ ++ +++ P-0233 +++ ++ +++ P-0234 +++ ++ +++ P-0235 +++ + +++ P-0236 +++ ++ +++ P-0237 +++ ++ +++ P-0238 +++ ++ +++ P-0239 +++ + ++ P-0240 +++ + +++ P-0241 +++ + +++ P-0242 ++ + ++ P-0243 ++ ++ ++ P-0244 ++ ++ ++ P-0245 +++ + +++ P-0246 ++ + ++ P-0247 +++ + +++ P-0248 + + + P-0249 +++ + +++ P-0250 +++ + +++ P-0251 +++ + +++ P-0252 +++ + +++ P-0253 +++ + +++ P-0254 +++ ++ +++ P-0255 +++ ++ +++ P-0256 +++ + +++ P-0257 +++ + +++ P-0258 +++ ++ +++ P-0259 +++ ++ +++ P-0260 +++ ++ +++ P-0261 +++ ++ +++ P-0262 +++ ++ +++ P-0263 +++ ++ +++ P-0264 +++ ++ +++ P-0265 +++ ++ +++ P-0266 +++ ++ +++ P-0267 +++ ++ +++ P-0268 +++ ++ +++ P-0269 +++ ++ +++ P-0270 ++ + ++ P-0271 +++ + +++ P-0272 +++ + +++ P-0273 +++ ++ +++ P-0274 +++ ++ +++ P-0275 +++ ++ +++ P-0276 +++ ++ +++ P-0277 +++ ++ +++ P-0278 +++ ++ +++ P-0279 +++ ++ +++ P-0280 +++ + +++ P-0281 +++ ++ +++ P-0282 +++ +++ +++ P-0283 +++ ++ +++ P-0284 +++ + +++ P-0285 +++ + +++ P-0286 +++ + +++ P-0287 +++ ++ +++ P-0288 +++ ++ +++ P-0289 +++ ++ +++ P-0290 +++ + +++ P-0291 +++ + +++ P-0292 +++ ++ +++ P-0293 +++ ++ +++ P-0294 +++ +++ +++ P-0295 +++ ++ +++ P-0296 +++ + +++ P-0297 +++ + +++ P-0298 +++ ++ +++ P-0299 +++ ++ +++ P-0300 +++ + +++ P-0301 +++ + +++ P-0302 +++ + +++ P-0303 +++ + +++ P-0304 +++ ++ +++ P-0305 +++ + +++ P-0306 +++ + +++ P-0307 +++ ++ +++ P-0308 +++ ++ +++ P-0309 +++ + +++ P-0310 +++ ++ +++ P-0311 +++ ++ +++ P-0312 +++ + +++ P-0313 +++ ++ +++ P-0314 +++ +++ +++ P-0315 +++ +++ +++ P-0316 +++ ++ +++ P-0317 +++ + +++ P-0318 +++ +++ +++ P-0319 +++ ++ +++ P-0320 +++ ++ +++ P-0321 +++ ++ +++ P-0322 +++ ++ +++ P-0323 +++ ++ +++ P-0324 +++ ++ +++ P-0325 +++ + +++ P-0326 +++ + +++ P-0327 +++ ++ +++ P-0328 +++ + +++ P-0329 +++ ++ +++ P-0330 +++ ++ +++ P-0331 +++ +++ +++ P-0332 +++ ++ +++ P-0333 +++ + +++ P-0334 +++ + +++ P-0335 +++ + +++ P-0336 +++ + +++ P-0337 +++ + +++ P-0338 +++ + +++ P-0339 +++ ++ +++ P-0340 +++ + +++ P-0341 +++ + +++ P-0342 +++ + +++ P-0343 +++ + +++ P-0344 +++ + +++ P-0345 +++ + +++ P-0346 +++ + +++ P-0347 +++ + +++ P-0348 +++ + +++ P-0349 +++ + +++ P-0350 +++ + +++ P-0351 +++ + +++ P-0352 +++ ++ +++ P-0353 +++ + +++ P-0354 +++ + +++ P-0355 +++ ++ +++ P-0356 +++ ++ +++ P-0357 +++ + +++ P-0358 +++ ++ +++ P-0359 +++ + +++ P-0360 +++ + +++ P-0361 +++ + +++ P-0362 +++ +++ +++ P-0363 +++ ++ +++ P-0364 +++ ++ +++ P-0365 +++ ++ +++ P-0366 +++ + +++ P-0367 +++ ++ +++ P-0368 +++ + +++ P-0369 +++ ++ +++ P-0370 +++ ++ +++ P-0371 +++ ++ +++ P-0372 +++ ++ +++ P-0373 +++ + +++ P-0374 +++ + +++ P-0375 +++ + +++ P-0376 +++ + +++ P-0377 +++ ++ +++ P-0378 +++ +++ +++ P-0379 +++ + +++ P-0380 +++ + +++ P-0381 +++ ++ +++ P-0382 +++ ++ +++ P-0383 +++ + +++ P-0384 +++ ++ +++ P-0385 +++ + +++ P-0386 +++ ++ +++ P-0387 +++ + +++ P-0388 +++ ++ +++ P-0389 +++ ++ +++ P-0390 +++ ++ +++ P-0391 +++ ++ +++ P-0392 +++ ++ +++ P-0393 +++ ++ +++ P-0394 +++ ++ +++ P-0395 +++ ++ +++ P-0396 +++ ++ +++ P-0397 +++ + +++ P-0398 +++ + +++ P-0399 +++ ++ +++ P-0400 +++ ++ +++ P-0401 +++ ++ +++ P-0402 +++ ++ +++ P-0403 +++ + +++ P-0404 +++ + +++ P-0405 +++ ++ +++ P-0406 +++ + +++ P-0407 +++ + +++ P-0408 +++ + +++ P-0409 +++ ++ +++ P-0410 +++ + +++ P-0411 +++ + +++ P-0412 +++ ++ +++ P-0413 +++ ++ +++ P-0414 +++ ++ +++ P-0415 +++ + +++ P-0416 +++ + +++ P-0417 +++ + +++ P-0418 +++ +++ +++ P-0419 +++ +++ +++ P-0420 +++ + +++ P-0421 +++ + +++ P-0422 +++ + +++ P-0423 +++ ++ +++ P-0424 +++ ++ +++ P-0425 +++ + +++ P-0426 +++ ++ +++ P-0427 +++ ++ +++ P-0428 +++ +++ +++ P-0429 +++ + +++ P-0430 +++ ++ +++ P-0431 +++ ++ +++ P-0432 +++ + +++ P-0433 +++ + +++ P-0434 +++ ++ +++ P-0435 +++ + +++ P-0436 +++ ++ +++ P-0437 +++ ++ +++ P-0438 +++ + +++ P-0439 +++ +++ +++ P-0440 ++ + ++ P-0441 +++ +++ +++ P-0442 +++ + +++ P-0443 +++ ++ +++ P-0444 +++ ++ +++ P-0445 +++ + +++ P-0446 +++ + +++ P-0447 +++ + +++ P-0448 +++ ++ +++ P-0449 +++ ++ +++

All patents and other references cited in this specification indicate the skill level of those who are familiar with the technology involved in the present invention, and are incorporated to the same extent by way of full citation, including any tables and figures, as if each reference was individually in full The way of citation is generally incorporated into this article.

Those skilled in the art should easily understand that the present invention is fully suitable for obtaining the mentioned objects and advantages as well as the inherent objects and advantages. The present invention as the embodiment described herein represents that the described methods, variations and compositions are exemplary and are not intended to limit the scope of the present invention. Those who are familiar with the technology in the field will think of the changes and other uses that are included in the spirit of the present invention and defined by the scope of the patent application.

It will be readily apparent to those skilled in the art that the content of the invention disclosed herein can be substituted and modified in various ways without departing from the scope and spirit of the invention. For example, changes can be made to provide other compounds of the compounds of the invention and/or various methods of administration can be used. Therefore, such other embodiments belong to the scope of the present invention and the scope of the following patent applications.

The invention illustratively described herein can be suitably practiced in the absence of any element or elements, limitation or limitations not specifically disclosed herein. The used terms and expressions are used as descriptive rather than limiting terms, and the use of the terms and expressions is not intended to exclude any equivalent features or parts of the displayed and described features, but it should be recognized that the scope of the claims of the present invention Inside, various improvements are possible. Therefore, it should be understood that although the present invention has been specifically described by the embodiments and optional features selected as appropriate, those skilled in the art can adopt modifications and variations of the concepts disclosed herein, and such modifications and variations The form should be regarded as belonging to the scope of the invention as defined by the scope of the attached patent application.

In addition, if the features or aspects of the present invention are described in terms of groups of alternatives, those skilled in the art should realize that the present invention also relates to any individual member or subgroup of members of the group described herein. description.

In addition, unless indicated to the contrary, if various values are provided for use in the embodiments, other embodiments are described by using any two different values as the endpoints of the range. Such ranges also belong to the scope of the present invention.

Therefore, other embodiments belong to the scope of the present invention and the scope of the following patent applications.

no

no

Claims (37)

A compound of formula I,

Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog thereof, wherein: A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is CH, X ² is C and X ³ is N; or A ¹ is R ⁶ , A ² is R ⁷ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is CH, X ² is C and X ³ is CH; or A ¹ is R ⁶ , A ^{2 is} not present, A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is CH, X ² is N and X ³ is CH; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, X ² is C and X ³ is CH; or A ¹ is R ⁷ , A ² is R ⁶ , A ³ is R ⁵ , A ⁴ is -LR ¹ , X ¹ is N, X ² is C and X ³ is CH; L is a bond, -CH ₂ -CH ₂ -, -(CH ₂ ) _1-2 -CH=CH-(CH ₂ ) _0-1 -, -CR ² R ³ -, -C(O)- or -S(O) ₂ -; the restriction is when A ¹ is R ⁷ , A ² is R ⁶ , A ³ is -LR ¹ , A ⁴ is R ⁵ , X ¹ is N, X ² is C and X ³ is C, then L is a bond; L ² is a bond or -C (R ¹³ ) ₂ -; R ¹ is phenyl, 5-9 membered heteroaryl, C ₃ -C ₆ cycloalkyl, C ₅ -C ₆ cycloalkenyl, 4-9 membered heterocycloalkyl or 5- 6-membered heterocycloalkenyl, where R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups; R ² is H, C ₁ -C ₆ alkyl or OH; R ³ is H, C ₁ -C ₆ alkyl, C ₁ -C ₆ cyanoalkyl, C ₁ -C ₆ haloalkyl, C ₃ -C ₆ cycloalkyl or 5-6 membered heteroaryl; R ⁴ is H, OH , C ₁ -C ₆ alkyl or C ₁ -C ₆ haloalkyl; when connected to carbon, R ⁵ is 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl, 5-9 membered Heteroaryl, 5-6 membered heterocycloalkyl,

or

, Wherein the 4-6 membered cycloalkyl group, 5-6 membered cycloalkenyl group, phenyl group or 5-9 membered heteroaryl group is optionally connected to ^{a -L 2 -J 1} group and 0-4 J ² Group substitution, the restriction is that J ^{1 is} directly bonded to a carbon atom; or when connected to nitrogen, R ⁵ is 4-6 membered cycloalkyl, 5-6 membered cycloalkenyl, phenyl or 5-9 membered hetero An aryl group, wherein the 4-6 membered cycloalkyl group, 5-6 membered cycloalkenyl group, phenyl group or 5-9 membered heteroaryl group is optionally connected to ^{1 -L 2} -J 1 group and 1-4 A J ² group is substituted, and the restriction is that J ^{1 is} directly bonded to a carbon atom; R ⁶ is a five-membered heteroaryl group containing at least one nitrogen atom, wherein the 5-membered heteroaryl group is optionally subjected to 0-2 R ⁸ group substitution; R ⁷ is H, halo or C ₁ -C ₆ alkyl; R ⁸ is C ₁ -C ₆ alkyl or C ₁ -C ₃ alkoxy C ₁ -C ₃ alkylene; each R ^{10 is} independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl or cyclopropyl; each R ^{11 is} independently H, C ₁ -C ₆ alkyl or C ₁ -C ₆ halo Alkyl group, or two R ¹¹ groups and the carbon atoms to which the two R ¹¹ groups are connected are connected together to form a cyclopropyl group; each R ^{12 is} independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ hydroxyalkyl or C ₁ -C ₆ haloalkyl; each R ^{13 is} independently H, CH ₃ or F, or each R ¹³ and the carbon atom to which it is attached together form a C ₃ -C ₆ cycloalkyl; R ¹⁴ is H, C ₁ -C ₆ alkyl or C ₁ -C ₃ alkoxy C ₁ -C ₃ alkylene; G ¹ is CN, C ₂ -C ₆ alkenyl, C ₁ -C ₆ cyano Alkyl, C ₁ -C ₆ cyanoalkylethynylene, C ₂ -C ₆ alkenyl, C ₁ -C ₆ alkylene, C ₁ -C ₆ alkylsulfonyl, C ₁ -C ₆ alkylsulfonyl C ₁ -C ₆ alkylene group, -N(R ¹⁰ ) ₂ , di-C ₁ -C ₆ alkylamino group C ₁ -C ₆ alkylene group, C ₁ -C ₆ alkylamino group C ₁ -C ₆ alkylene, amino C ₁ -C ₆ alkylene, -C(O)-C ₁ -C ₆ alkyl, -C(O)-C ₁ -C ₆ hydroxyalkyl, -C( O)-C ₁ -C ₆ haloalkyl, -C(O)OR ¹² , -C ₁ -C ₃ alkylene-C(O)OR ¹² , -C(O)-N(H)-C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₆ alkylene, C ₃ -C ₆ cycloalkyl, C ₂ -C ₆ alkynylene, 4-6 membered heterocycloalkyl, -C(O)-N(R ¹⁰ ) ₂ , -C ₁ -C ₆ alkylene-C(O)-N(R ¹⁰ ) ₂ or phenyl C ₁ -C ₆ alkoxy, with the proviso that when G ¹ is connected to a nitrogen atom When G ^{1 is} not CN; each G ^{2 is} independently CN, halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ Haloalkoxy, OH, pendant oxy, C ₁ -C ₆ hydroxyalkyl, the restriction is that when G ^{2 is} connected to a nitrogen atom, G ^{2 is} not CN, halo, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy or OH; J ¹ is -C(R ¹¹ ) ₂ -C(O)OH, -C(O)OH, -C(O)OC ₁ -C ₆ alkyl,- CH ₂ -C(O)OC ₁ -C ₆ alkyl group, -C(O)N(R ¹⁰ ) ₂ , -C(O)N(H)-CN, -C(O)N(H)OH, -C(O)N(H)-SO ₂ -C ₁ -C ₆ alkyl, -N(H)-SO ₂ -C ₁ -C ₆ alkyl, C ₁ -C ₆ alkylsulfonyl, tetra Azole group or -S(O) ₂ -N(R ¹⁰ ) ₂ ; and each J ^{2 is} independently 4-6 membered heterocycloalkyl, -O-(4-6 membered heterocycloalkyl), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl alkoxy, phenyl C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halo, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, OH, C ₁ -C ₆ hydroxyalkyl, CN, C ₁ -C ₆ cyanoalkyl, C ₂ -C ₆ alkynyl, C ₃ -C ₆ cycloalkylethynylene, C ₃ -C ₆ cycloalkyl, 4-6 membered heterocycloalkyl, NO ₂ or -N(R ¹⁰ ) ₂ , with the restriction that when J ^{2 is} connected to nitrogen , J ^{2 is} not -O-(4-6 membered heterocycloalkyl), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl alkoxy, phenyl C ₁ -C ₆ alkoxy Group, C ₁ -C ₆ alkoxy, halo, C ₁ -C ₆ haloalkoxy, OH, CN, C ₂ -C ₆ alkynyl, C ₃ -C ₆ cycloalkylethynylene or -N( R ¹⁰ ) ₂ . The compound of claim 1 , wherein: R ¹ is a phenyl group, a 5-6 membered heteroaryl group, a C ₃ -C ₆ cycloalkyl group, a C ₅ -C ₆ cycloalkenyl group, a 4-6 membered heterocycloalkyl group or 5-6 membered heterocycloalkenyl, where R ^{1 is} optionally substituted with 1 G ¹ group and 1-3 G ² groups; R ³ is H, C ₁ -C ₆ alkyl, C ₁ -C ₆ Cyanoalkyl, C ₁ -C ₆ haloalkyl, C ₃ -C ₆ cycloalkyl or 5-6 membered heteroaryl; R ⁴ is H, OH, C ₁ -C ₂ alkyl or C ₁ -C ₂ haloalkyl; when connected to carbon, R ⁵ is 4-6 membered cycloalkyl, cyclohexenyl, phenyl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl,

or

, Wherein the 4-6 membered cycloalkyl group, cyclohexenyl group, phenyl group, 5-6 membered heteroaryl group or 5-6 membered heterocycloalkyl group each optionally has a J ¹ group and 0-4 J ² group substitution, the restriction is that the J ^{1 is} directly bonded to a carbon atom; or when connected to nitrogen, R ⁵ is 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5-6 membered Heteroaryl groups, wherein the 4-6 membered cycloalkyl, cyclohexenyl, phenyl or 5-6 membered heteroaryl groups each have 1 -L ² -J ¹ group and 1-4 J ² group substitution, the restriction is that J ^{1 is} directly bonded to a carbon atom; R ⁶ is a five-membered heteroaryl group containing at least one nitrogen atom, wherein the heteroaryl group is optionally substituted ^{with 1-2 R 8 groups} ; R ⁷ is H, halo or C ₁ -C ₅ alkyl; R ⁸ is C ₁ -C ₄ alkyl or C ₁ -C ₂ alkoxy C ₁ -C ₂ alkylene; each R ^{10 is} independently Is H, C ₁ -C ₅ alkyl, C ₁ -C ₅ haloalkyl or cyclopropyl; each R ^{11 is} independently H, C ₁ -C ₅ alkyl or C ₁ -C ₅ haloalkyl, or Two R ¹¹ groups are connected with the carbon atoms to which the two R ¹¹ are connected to form a cyclopropyl group; each R ¹² is H; R ¹⁴ is H, C ₁ -C ₅ alkyl or C ₁ -C ₃ Alkoxy C ₁ -C ₃ alkylene; G ¹ is CN, C ₁ -C ₆ cyanoalkyl, C ₁ -C ₅ cyanoalkylethynylene, C ₂ -C ₅ alkenyl C ₁ -C ₅ alkylene, C ₁ -C ₅ alkylsulfonyl, C ₁ -C ₅ alkylsulfonyl, C ₁ -C ₅ alkylene, -N(R ¹⁰ ) ₂ , di-C ₁ -C ₅ Alkylamino group -C ₁ -C ₅ alkylene group, C ₁ -C ₅ alkylamino group -C ₁ -C ₅ alkylene group, amino group C ₁ -C ₅ alkylene group, -C(O)- C ₁ -C ₅ alkyl, -C(O)-C ₁ -C ₅ hydroxyalkyl, -C(O)-C ₁ -C ₅ haloalkyl, -C(O)OR ¹² , -C _1- C ₃ alkylene-C(O)OR ¹² , -C(O)-N(H)-C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl C ₁ -C ₅ alkylene, C ₃ -C ₆ cycloalkyl, C ₂ -C ₅ alkynylene, 4-6 membered heterocycloalkyl, -C(O)-N(R ¹⁰ ) ₂ , -C _1- C ₅ alkylene-C(O)-N(R ¹⁰ ) ₂ or phenyl C ₁ -C ₅ alkoxy, with the restriction that when G ^{1 is} connected to a nitrogen atom, G ^{1 is} not CN; each G ^{2 is} independently halo, C ₁ -C ₅ alkyl, C ₁ -C ₅ haloalkyl, C ₁ -C ₅ alkoxy, C ₁ -C ₅ haloalkoxy, OH, pendant oxy, C ₁ -C ₅ hydroxyalkyl, the restriction is when G ^{2 is} connected to the nitrogen atom , G ^{2 is} not a halo, C ₁ -C ₅ alkoxy, C ₁ -C ₅ haloalkoxy or OH; J ¹ is -C(R ¹¹ ) ₂ -C(O)OH, -C(O )OH, -C(O)OC ₁ -C ₅ alkyl, -CH ₂ -C(O)OC ₁ -C ₅ alkyl, -C(O)N(R ¹⁰ ) ₂ , -C(O)N (H)-CN, -C(O)N(H)OH, -C(O)N(H)-SO ₂ -C ₁ -C ₅ alkyl, -N(H)-SO ₂ -C _1- C ₅ alkyl, C ₁ -C ₅ alkylsulfonyl, tetrazolyl or -S(O) ₂ -N(R ¹⁰ ) ₂ ; and each J ^{2 is} independently 4-6 membered heterocycloalkyl, -O-(4-6 membered heterocycloalkyl), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl alkoxy, phenyl C ₁ -C ₅ alkoxy, C _1- C ₅ alkyl, C ₁ -C ₅ alkoxy, halo, C ₁ -C ₅ haloalkyl, C ₁ -C ₅ haloalkoxy, OH, C ₁ -C ₅ hydroxyalkyl, CN, C ₁ -C ₅ cyanoalkyl, C ₂ -C ₅ alkynyl, C ₃ -C ₆ cycloalkylethynylene, C ₃ -C ₆ cycloalkyl, 4-6 membered heterocycloalkyl or -N(R ¹⁰ ) ₂ , the restriction is that when J ^{2 is} connected to nitrogen, J ^{2 is} not -O-(4-6 membered heterocycloalkyl), -OC ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkane Group alkoxy, phenyl C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkoxy, halo, C ₁ -C ₅ haloalkoxy, OH, CN, C ₂ -C ₆ alkynyl, C ₃ -C ₆ cycloalkylethynylene or -N(R ¹⁰ ) ₂ . Such as the compound of claim 1 or claim 2, which has formula II(a), II(b) or II(c)

, Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog thereof. A compound according to any one of the preceding claims, which has any one of formula III(a), III(c), III(d), III(e) or III(f):

, Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analogue thereof. The compound of any one of the preceding claims, wherein R ⁶ is:

. The compound of any one of the preceding claims, wherein R ⁶ is:

. A compound according to any one of the preceding claims, wherein R ⁴ is H, OH, CF ₃ or CH ₃ . The compound of any one of 2, 3, 5, 6, or 7, wherein L is a bond, -CH ₂ -, -(CH ₂ ) ₂ -, CH(CH ₃ )-, CH(CH ₂ CH ₃ )- , -C(O)-, -CH(C ₃ -C ₆ cycloalkyl)-, -CH(pyridyl)-, -C(CH ₃ )(pyridyl)-, -S(O) ₂ -or -C(H)(CH ₂ CN)-. A compound according to any one of the preceding claims, wherein R ¹ is phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazolyl, C ₃ -C ₆ cycloalkyl, cyclohexenyl, morpholinyl, Piperazinyl, piperidinyl, pyrrolidinyl, tetrahydro-2H-furanyl, oxetanyl, azetidine, tetrahydro-2H-piperanyl, 1,1-tetrahydrodioxide -2H-thiopiperanyl, 1-oxytetrahydro-2H-thiopiperanyl, tetrahydro-2H-thiopiperanyl, tetrahydrothienyl or thienyl, where R ^{1 is} optionally connected to 1 G ¹ group Group and 1-3 G ² groups. The compound of any one of the preceding claims, wherein: R ¹ is (a), (b), (c), (d), (e), (f), (g), (h), (i) ), (j), (k), (l) or (m): (a) _{C 3} -C ₆ ^{cycloalkyl substituted with 1-3 G 2} groups as appropriate, where G ² Is F, CN or -CH ₂ CN; (b) ^{phenyl substituted by 1 G 1} group and 1-3 G ² groups as appropriate, where G ¹ is benzyloxy, -C(=CH ₂ ) CH ₃ , -C(O)OH, -C(O)NH ₂ , -C(O)N(H)-cyclopropyl, cyclopropyl, CN or -SO ₂ CH ₃ ; and each G ² Independently -OCHF ₂ , Cl, F, -OCH ₃ , -OCF ₃ , CH ₃ , CF ₃ and -C(CH ₃ ) ₂ -OH; (c) As appropriate, through 1 G ¹ group and 1- Pyridyl substituted with two G ² groups, where G ¹ is -C(O)OH, -C(O)NH ₂ , cyclopropyl or cyclopropyl alkynylene; and each G ^{2 is} independently F, CN , OCH ₃ , CF ₃ , CH ₃ , OH, -CH(CH ₃ ) ₂ and Cl; (d) ^{pyrazolyl substituted with 1 G 1} group and 1-2 G ² groups as appropriate, restricted The condition is that when R ¹ is a pyrazolyl group, L is a bond, and G ¹ that can replace the hydrogen atom of -NH- or =CH- is -CH ₂ -SO ₂ -CH ₃ , -(CH ₂ ) _2- N(CH ₃ ) ₂ , cyclopropyl, -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN or -CH ₂ C(O)N(CH ₃ ) ₂ ; and can replace -NH- or = each CH- hydrogen atoms of G ² is independently C ₁ -C ₆ alkyl, halo C ₁ -C ₆ alkyl and hydroxy C ₁ -C ₆ alkyl; (e) optionally substituted with -NH _2, -N (CH ₃ ) ₂ , OCH ₃ , n-azetidinyl or cyclopropyl substituted pyrimidinyl; (f) pyridazinyl; (g) 1-2 of them are independently C _1- Tetrahydro-2H-piperanyl substituted with C ₆ alkyl, C ₁ -C ₆ haloalkyl, hydroxy C ₁ -C ₆ alkyl, Cl and F; (h) 1-2 as the case may be Each independently is a C ₁ -C ₆ alkyl group, a C ₁ -C ₆ haloalkyl group, a hydroxy C ₁ -C ₆ alkyl group, a tetrahydro-2H-furan group substituted with a group of Cl and F; (i) as In the case of morpholinyl substituted by 1-2 groups each independently being C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl and hydroxy C ₁ -C ₆ alkyl; (j) oxo heterocycle Butanyl group; (k) 1-2 independently C ₁ -C ₆ alkyl group, C ₁ -C ₆ haloalkyl group and hydroxy C ₁ -C ₆ alkyl group substituted piperidinyl group; (1) 1-2 C ₁ -C ₆ alkyl group, C ₁ -C ₆ haloalkyl group, C 1 -C 6 haloalkyl group, hydroxy C ₁ -C ₆ Cyclohexenyl substituted by alkyl, Cl and F groups; or (m) thienyl. The compound of any one of claims 1 to 7 ^{, wherein: -LR 1} is:

, Where: G ³ is H, OCH ₃ , N-azetidinyl, NH ₂ , -N(CH ₃ ) ₂ , cyclopropyl; G ⁴ is H, CH ₃ , -CH ₂ CH ₃ ,- (CH ₂ )N(CH ₃ ) ₂ , -CH ₂ -SO ₂ -CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ C(CH ₃ ) ₂ (OH), cyclopropyl, -CH _2- Cyclopropyl, -(CH ₂ ) ₂ -CN or -CH ₂ C(O)N(CH ₃ ) ₂ ; G ⁵ is H or OH; G ⁶ is H or CH ₃ ; and G ⁷ is H, CH ₃ , -(CH ₂ )N(CH ₃ ) ₂ , -SO ₂ -CH ₃ , -CH ₂ -SO ₂ -CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ C(CH ₃ ) ₂ (OH) , Cyclopropyl, -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -CH ₂ C(O)N(CH ₃ ) ₂ , -C(O)OC(CH ₃ ) ₃ , -C (O)CH ₃ or -C(O)C(CH ₃ ) ₃ . Such as the compound of claim 11 , wherein: G ¹ is benzyloxy, -C(=CH ₂ )CH ₃ , -C(O)OH, -C(O)NH ₂ , -C(O)N(H )-Cyclopropyl, cyclopropyl, -CH ₂ -cyclopropyl, cyclopropylalkynylene, -CH ₂ -SO ₂ -CH ₃ , -SO ₂ -CH ₃ , -(CH ₂ )N(CH ₃ ) ₂ , -(CH ₂ ) ₂ -N(CH ₃ ) ₂ , -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -C(O)OC(CH ₃ ) ₃ , -C(O ) CH ₃ and -C(O)C(CH ₃ ) ₃ , -CH ₂ C(O)N(CH ₃ ) ₂ , CN or -SO ₂ CH ₃ ; and each G ^{2 is} independently -OCHF ₂ ,- OCH ₂ F, Cl, F, -OCH ₃ , OH, -OCF ₃ , CH ₃ , -CH(CH ₃ ) ₂ , CF ₃ , -CH ₂ CN, CH ₂ C(CH ₃ ) ₂ (OH) and- C(CH ₃ ) ₂ -OH. Such as the compound of claim 1 , where: -LR ¹ is:

. Such as the compound of claim 13 ^{, wherein G 1} is benzyloxy, -C(=CH ₂ )CH ₃ , -C(O)OH, -C(O)NH ₂ , -C(O)N(H) -Cyclopropyl, cyclopropyl, -CH ₂ -cyclopropyl, cyclopropyl alkynylene, -CH ₂ -SO ₂ -CH ₃ , -SO ₂ -CH ₃ , -(CH ₂ )N(CH ₃ ) ₂ , -(CH ₂ ) ₂ -N(CH ₃ ) ₂ , -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -C(O)OC(CH ₃ ) ₃ , -C(O) CH ₃ , -C(O)C(CH ₃ ) ₃ , -CH ₂ C(O)N(CH ₃ ) ₂ , CN or -SO ₂ CH ₃ ; and each G ^{2 is} independently -OCHF ₂ , -OCH ₂ F, Cl, F, -OCH ₃ , OH, -OCF ₃ , CH ₃ , -CH(CH ₃ ) ₂ , CF ₃ , -CH ₂ CN, CH ₂ C(CH ₃ ) ₂ (OH) and -C (CH ₃ ) ₂ -OH. A compound according to any one of the preceding claims, wherein when connected to a carbon, R ⁵ is:

. The compound of any one of claims 1 to 14 ^{, wherein R 5} is:

. The compound of any one of claims 1 to 14 ^{, wherein R 5} is:

. The compound of any one of claims 1 to 14 ^{, wherein R 5} is:

. Such as the compound of any one of claims 15 to 18 ^{, wherein: J 1} is -C(O)OH, -C(O)OCH ₃ , -CH ₂ C(O)OH, -C(O)N(H )CH ₃ , -C(O)NH ₂ , tetrazolyl, -SO ₂ CH ₃ , -C(O)N(H)CN, C(O)N(H)OH, -SO ₂ NH ₂ ,- SO ₂ NH-cyclopropyl, -C(O)N(H)SO ₂ CH ₃ ; and each J ^{2 is} independently -O-cyclobutyl, -OCH ₂ -phenyl, -O-cyclopropyl, -O-CH ₂ -Cyclopropyl, cyclopropylethynylene, CN, OH, cyclopropyl, F, Cl, -OCH ₃ , -OCHF ₂ , OCF ₃ , -OCH ₂ CF ₃ , -OCH ₂ CHF ₂ , -OCH(CH ₃ ) ₂ , -CH ₂ CH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ and CH ₃ . Such as the compound of claim 19 , wherein: J ¹ is -C(O)OH or -C(O)OCH ₃ ; and each J ^{2 is} independently F, Cl, -OCH ₃ , -OCHF ₂ , OCF ₃ ,- OCH ₂ CF ₃ , -OCH ₂ CHF ₂ , -OCH(CH ₃ ) ₂ , -CH ₂ CH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ and CH ₃ . Such as the compound of claim 1 , which has formula IV(a) or IV(c):

Or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or deuterated analog thereof, wherein: R ⁵ is:

; J ¹ is -C(O)OH or -C(O)OCH ₃ ; each J ^{2 is} independently F, Cl, -OCH ₃ , -OCHF ₂ , OCF ₃ , -OCH ₂ CF ₃ , -OCH ₂ CHF ₂ , -OCH(CH ₃ ) ₂ , -CH ₂ CH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ and CH ₃ ; -LR ¹ is

Where G ¹ is benzyloxy, -C(=CH ₂ )CH ₃ , -C(O)OH, -C(O)NH ₂ , -C(O)N(H)-cyclopropyl, cyclopropyl Group, -CH ₂ -cyclopropyl, cyclopropylalkynylene, -CH ₂ -SO ₂ -CH ₃ , -SO ₂ -CH ₃ , -(CH ₂ )N(CH ₃ ) ₂ , -(CH ₂ ) ₂ -N(CH ₃ ) ₂ , -CH ₂ -cyclopropyl, -(CH ₂ ) ₂ -CN, -C(O)OC(CH ₃ ) ₃ , -C(O)CH ₃ , -C(O )C(CH ₃ ) ₃ , -CH ₂ C(O)N(CH ₃ ) ₂ , CN or -SO ₂ CH ₃ ; and each G ^{2 is} independently -OCHF ₂ , -OCH ₂ F, Cl, F, -OCH ₃ , OH, -OCF ₃ , CH ₃ , -CH(CH ₃ ) ₂ , CF ₃ , CN, -CH ₂ CN, CH ₂ C(CH ₃ ) ₂ (OH) and -C(CH ₃ ) ₂ -OH. A compound selected from Table 1, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising the compound according to any one of the preceding claims and a pharmaceutically acceptable carrier. The pharmaceutical composition of claim 23 , which further comprises a second agent. A method for treating an individual suffering from a disease or condition mediated by EP300 or CBP, the method comprising administering to the individual an effective amount of a compound according to any one of claims 1 to 22, or a medicine thereof Academically acceptable salts, deuterated analogs, tautomers or stereoisomers, or pharmaceutical compositions as claimed in any one of claims 23 to 24. The method for treating a disease or condition according to claim 25 , wherein the disease or condition is a cancer with an inactivating mutation in CBP or EP300, or a cancer with activation of EP300 or CBP in it. The method for treating a disease or condition according to claim 25 , wherein the disease or condition is cancer that expresses an androgen receptor. The method for treating a disease or condition according to claim 25 , wherein the disease or condition is a neoplastic disorder, cancer, an age-related disease, an inflammatory disorder, a cognitive disorder, or a neurodegenerative disease. The method for treating a disease or condition according to claim 25 , wherein the disease or condition is acral lentigo melanoma, acute eosinophilic leukemia, acute erythrocyte leukemia, acute lymphoblastic leukemia, acute Megakaryoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, bladder cancer, adenocarcinoma, adult T-cell leukemia/lymphoma, aggressive NK-cell leukemia, AIDS-related lymphoma, pleomorphic large cell Lymphoma, Angioimmunoblastic T-cell lymphoma, B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, B-cell lymphoma, bone cancer, Burkitt’s lymphoma, skin T cells Lymphoma, colorectal cancer, diffuse large B-cell lymphoma, enteropathy-associated T-cell lymphoma, follicular lymphoma, glioblastoma multiforme, glioma, gastric cancer, hepatosplenic T-cell lymphoma , Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, small cell lung cancer, non-small cell lung cancer , MALT lymphoma, malignant peripheral nerve sheath tumor, mantle cell lymphoma, marginal zone B-cell lymphoma, mast cell leukemia, breast cancer, neuroblastoma, melanoma, Merkel cell cancer, Mesothelioma, multiple myeloma, neuroblastoma, neurofibroma, nodular melanoma, osteosarcoma, ovarian cancer, precursor T-lymphoblastic lymphoma, primary central nervous system lymphoma, progenitor Primary exudative lymphoma, prostate cancer, pancreatic cancer, skin cancer, T-cell lymphoma, uveal melanoma, Alzheimer's disease, Parkinson's disease, or colorectal cancer. The method of claim 29 , wherein the disease or condition is small cell lung cancer, non-small cell lung cancer, bladder cancer, non-Hodgkin's lymphoma, acute myelogenous leukemia, multiple myeloma, diffuse large B cell Lymphoma, breast cancer or prostate cancer. The method of claim 29 , wherein the disease or condition is Alzheimer's disease or Parkinson's disease. The method according to any one of claims 25 to 31 , which further comprises administering one or more other therapeutic agents. The method of claim 32 , wherein the one or more other therapeutic agents are one or more of the following: i) an alkylating agent selected from the group consisting of adozelesin, altretamine, Bizelesin, busulfan, carboplatin, carboquone, carmustine, chlorambucil, cisplatin , Cyclophosphamide, dacarbazine, estramustine, fotemustine, hepsulfam, ifosfamide, improxide Improsulfan, irofulven, lomustine, mechlorethamine, melphalan, oxaliplatin, piposulfan , Semustine, streptozocin, temozolomide, thiotepa and treosulfan; ii) antibiotics selected from bleomycin (bleomycin) ), actinomycin D (dactinomycin), daunorubicin, cranberry (doxorubicin), epirubicin, idarubicin, menogaril, mitotic Mitomycin, mitoxantrone, neocarzinostatin, pentostatin and plicamycin; iii) antimetabolites, which are selected from the group consisting of Group: azacitidine, capecitabine, cladribine, clofarabine, cytarabine, decitabine, fluorourea Floxuridine, fludarabine, 5-fluorouracil, ftorafur, gemcitabine, hydroxyurea, mercaptopurine, methotrexate, naira Nelarabine, Pemetrexed (Pemetrexed), raltitrexed, thioguanine and trimetrexate; iv) an immunotherapeutic agent selected from PD-1 or PD-L1 inhibitors; v) hormones or hormones Antagonist, which is selected from the group consisting of enzalutamide, abiraterone, anastrozole, androgen, buserelin, diethylstilbestrol, Exemestane, flutamide, fulvestrant, goserelin, idoxifene, letrozole, leuprolide (Leuprolide), megestrol (magestrol), raloxifene, tamoxifen and toremifene; vi) taxane, which is selected from DJ-927, doxyl Docetaxel, TPI 287, paclitaxel and DHA-paclitaxel; vii) retinoids, which are selected from alitretinoin, bexarotene, fereti Fenretinide, isotretinoin and tretinoin; viii) alkaloids selected from etoposide, homoharringtonine, teniposide, Vinblastine (vinblastine), vincristine (vincristine), vindesine (vindesine) and vinorelbine (vinorelbine); ix) anti-angiogenesis agent selected from AE-941 (GW786034, Neovastat) , ABT-510, 2-Methoxyestradiol, lenalidomide and thalidomide; x) topoisomerase inhibitors, which are selected from amsacrine, acitrate Carin (edotecarin), exatecan (exatecan), irinotecan (irinotecan), SN-38 (7-ethyl-10-hydroxy-camptothecin), rubitecan (rubitecan), topotecan (Topotecan) and 9-aminocamptothecin (9-aminocamptothecin); xi) kinase inhibitor, which is selected from erlotinib, gefitinib (Gefitinib), flavopiridol, imatinib mesylate, lapatinib, sorafenib, sunitinib malate, AEE -788, AG-013736, AMG 706, AMN107, BMS-354825, BMS-599626, UCN-01 (7-hydroxy staurosporine), vemurafenib, dabrafenib, qu Trametinib, cobimetinib, selumetinib, and vatalanib; xii) a targeted signal transduction inhibitor, which is selected from bortezomib , Geldanamycin (geldanamycin) and rapamycin (rapamycin); xiii) biological response modifier, which is selected from imiquimod (imiquimod), interferon-α and interleukin-2; xiv) IDO Inhibitor; and xv) a chemotherapeutic agent selected from the group consisting of 3-AP (3-amino-2-hydroxyaldethiocarbazone), altrasentan, aminoglutethimide, ana Gray (anagrelide), asparaginase (asparaginase), bryostatin-1, cilengitide, elesclomol, eribulin mesylate mesylate (E7389), ixabepilone, lonidamine, masoprocol, mitoguanazone, oblimersen, sulindac ), testolactone, tiazofurin, mTOR inhibitor, PI3K inhibitor, Cdk4 inhibitor, Akt inhibitor, Hsp90 inhibitor, farnesyl transferase inhibitor or aromatase inhibitor (A Nastrozole letrozole exemestane (anastrozole letrozole exemestane)); xvi) Mek inhibitor; xvii) Tyrosine kinase inhibitor; xviii) c-Kit mutant inhibitor, xix) EGFR inhibitor, PD-1 Inhibitors or xx) epigenetic modulators. As requested item33 The method, wherein the one or more other therapeutic agents are epigenetic modulators, which are selected from the group consisting of: (A) DNA methyltransferase; (B) Histone or protein methyltransferase; (C) Histone demethylase; (D) Histone deacetylase inhibitors; (E) Histone acetyltransferase; (F) Other chromatin remodeling agents; and (G) BET inhibitor. The method of claim 34 , wherein the epigenetic modulator is a histone deacetylase inhibitor, which is selected from the group consisting of: vorinostat, romidepsin , Chidamide, Panobinostat, Belinostat, Valproic acid, Mocetinostat, Abexinostat, En Tennot (entinostat), Reminostat (resminostat), Givinostat (givinostat) and Quisinostat (quisinostat). The method of claim 34 , wherein the epigenetic modulator is a BRD4 inhibitor. The method of claim 33 , wherein the one or more other therapeutic agents are PD-1 inhibitors, quizartinib, enzalutamide, abiraterone, or BRD4 inhibitors.